An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.
Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate.
A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms. It may be present in higher organisms and has an intrinsic molecular activity only 5% of that of DNA Polymerase I. This polymerase has 3'-5' exonuclease activity, is effective only on duplex DNA with gaps or single-strand ends of less than 100 nucleotides as template, and is inhibited by sulfhydryl reagents. EC
The process by which a DNA molecule is duplicated.
DNA-dependent DNA polymerases found in bacteria, animal and plant cells. During the replication process, these enzymes catalyze the addition of deoxyribonucleotide residues to the end of a DNA strand in the presence of DNA as template-primer. They also possess exonuclease activity and therefore function in DNA repair.
Specific loci that show up during KARYOTYPING as a gap (an uncondensed stretch in closer views) on a CHROMATID arm after culturing cells under specific conditions. These sites are associated with an increase in CHROMOSOME FRAGILITY. They are classified as common or rare, and by the specific culture conditions under which they develop. Fragile site loci are named by the letters "FRA" followed by a designation for the specific chromosome, and a letter which refers to which fragile site of that chromosome (e.g. FRAXA refers to fragile site A on the X chromosome. It is a rare, folic acid-sensitive fragile site associated with FRAGILE X SYNDROME.)
Susceptibility of chromosomes to breakage leading to translocation; CHROMOSOME INVERSION; SEQUENCE DELETION; or other CHROMOSOME BREAKAGE related aberrations.
3-Hydroxy-4-oxo-1(4H)-pyridinealanine. An antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca.
A simple organophosphorus compound that inhibits DNA polymerase, especially in viruses and is used as an antiviral agent.
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
A DNA-dependent DNA polymerase characterized in prokaryotes and may be present in higher organisms. It has both 3'-5' and 5'-3' exonuclease activity, but cannot use native double-stranded DNA as template-primer. It is not inhibited by sulfhydryl reagents and is active in both DNA synthesis and repair. EC
A purine or pyrimidine base bonded to a DEOXYRIBOSE containing a bond to a phosphate group.
Compounds that inhibit cell production of DNA or RNA.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
An intermediate in the synthesis of cholesterol.
Cytosine nucleotides which contain deoxyribose as the sugar moiety.
A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms but may be present in higher organisms. Use also for a more complex form of DNA polymerase III designated as DNA polymerase III* or pol III* which is 15 times more active biologically than DNA polymerase I in the synthesis of DNA. This polymerase has both 3'-5' and 5'-3' exonuclease activities, is inhibited by sulfhydryl reagents, and has the same template-primer dependence as pol II. EC
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The rate dynamics in chemical or physical systems.
Established cell cultures that have the potential to propagate indefinitely.
Colored azo compounds formed by the reduction of tetrazolium salts. Employing this reaction, oxidoreductase activity can be determined quantitatively in tissue sections by allowing the enzymes to act on their specific substrates in the presence of tetrazolium salts.
Guanine nucleotides which contain deoxyribose as the sugar moiety.
A family of very small DNA viruses containing a single molecule of single-stranded DNA and consisting of two subfamilies: PARVOVIRINAE and DENSOVIRINAE. They infect both vertebrates and invertebrates.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Deoxyribonucleic acid that makes up the genetic material of viruses.
Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.
A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.

Involvement of p21 in the PKC-induced regulation of the G2/M cell cycle transition. (1/594)

Activation of protein kinase C (PKC) inhibits cell cycle progression at the G1/S and G2/M transitions. We found that phorbol 12-myristate 13-acetate (PMA) induced upregulation of p21, not only in MCF-7 cells arrested in the G1 phase as previously shown, but also in cells delayed in the G2 phase. This increase in p21 in cells accumulated in the G1 and G2/M phases of the cell cycle after PMA treatment was inhibited by the PKC inhibitor GF109203X. This indicates that PKC activity is required for PMA-induced p21 upregulation and cell cycle arrest in the G1 and G2/M phases of the cell cycle. To further assess the role of p21 in the PKC-induced G2/M cell cycle arrest independently of its G1 arrest, we used aphidicolin-synchronised MCF-7 cells. Our results show that, in parallel with the inhibition of cdc2 activity, PMA addition enhanced the associations between p21 and either cyclin B or cdc2. Furthermore, we found that after PMA treatment p21 was able to associate with the active Tyr-15 dephosphorylated form of cdc2, but this complex was devoid of kinase activity indicating that p21 may play a role in inhibition of cdc2 induced by PMA. Taken together, these observations provide evidence that p21 is involved in integrating the PKC signaling pathway to the cell cycle machinery at the G2/M cell cycle checkpoint.  (+info)

Cell cycle-dependent nuclear accumulation of the p94fer tyrosine kinase is regulated by its NH2 terminus and is affected by kinase domain integrity and ATP binding. (2/594)

p94fer and p51ferT are two tyrosine kinases that are encoded by differentially spliced transcripts of the FER locus in the mouse. The two tyrosine kinases share identical SH2 and kinase domains but differ in their NH2-terminal amino acid sequence. Unlike p94fer, the presence of which has been demonstrated in most mammalian cell lines analyzed, the expression of p51ferT is restricted to meiotic cells. Here, we show that the two related tyrosine kinases also differ in their subcellular localization profiles. Although p51ferT accumulates constitutively in the cell nucleus, p94fer is cytoplasmic in quiescent cells and enters the nucleus concomitantly with the onset of S phase. The nuclear translocation of the FER proteins is driven by a nuclear localization signal (NLS), which is located within the kinase domain of these enzymes. The functioning of that NLS depends on the integrity of the kinase domain but was not affected by inactivation of the kinase activity. The NH2 terminus of p94fer dictated the cell cycle-dependent functioning of the NLS of FER kinase. This process was governed by coiled-coil forming sequences that are present in the NH2 terminus of the kinase. The regulatory effect of the p94fer NH2-terminal sequences was not affected by kinase activity but was perturbed by mutations in the kinase domain ATP binding site. Ectopic expression of the constitutively nuclear p51ferT in CHO cells interfered with S-phase progression in these cells. This was not seen in p94fer-overexpressing cells. The FER tyrosine kinases seem, thus, to be regulated by novel mechanisms that direct their different subcellular distribution profiles and may, consequently, control their cellular functioning.  (+info)

Nucleo-cytoplasmic interactions that control nuclear envelope breakdown and entry into mitosis in the sea urchin zygote. (3/594)

In sea urchin zygotes and mammalian cells nuclear envelope breakdown (NEB) is not driven simply by a rise in cytoplasmic cyclin dependent kinase 1-cyclin B (Cdk1-B) activity; the checkpoint monitoring DNA synthesis can prevent NEB in the face of mitotic levels of Cdk1-B. Using sea urchin zygotes we investigated whether this checkpoint prevents NEB by restricting import of regulatory proteins into the nucleus. We find that cyclin B1-GFP accumulates in nuclei that cannot complete DNA synthesis and do not break down. Thus, this checkpoint limits NEB downstream of both the cytoplasmic activation and nuclear accumulation of Cdk1-B1. In separate experiments we fertilize sea urchin eggs with sperm whose DNA has been covalently cross-linked to inhibit replication. When the pronuclei fuse, the resulting zygote nucleus does not break down for >180 minutes (equivalent to three cell cycles), even though Cdk1-B activity rises to greater than mitotic levels. If pronuclear fusion is prevented, then the female pronucleus breaks down at the normal time (average 68 minutes) and the male pronucleus with cross-linked DNA breaks down 16 minutes later. This male pronucleus has a functional checkpoint because it does not break down for >120 minutes if the female pronucleus is removed just prior to NEB. These results reveal the existence of an activity released by the female pronucleus upon its breakdown, that overrides the checkpoint in the male pronucleus and induces NEB. Microinjecting wheat germ agglutinin into binucleate zygotes reveals that this activity involves molecules that must be actively translocated into the male pronucleus.  (+info)

The Drosophila ATM homologue Mei-41 has an essential checkpoint function at the midblastula transition. (4/594)

BACKGROUND: Drosophila embryogenesis is initiated by 13 rapid syncytial mitotic divisions that do not require zygotic gene activity. This maternally directed cleavage phase of development terminates at the midblastula transition (MBT), at which point the cell cycle slows dramatically, membranes surround the cortical nuclei to form a cellular blastoderm, and zygotic gene expression is first required. RESULTS: We show that embryos lacking Mei-41, a Drosophila homologue of the ATM tumor suppressor, proceed through unusually short syncytial mitoses, fail to terminate syncytial division following mitosis 13, and degenerate without forming cells. A similar cleavage-stage arrest is produced by mutations in grapes, which encodes a homologue of the Checkpoint-1 kinase. We present biochemical, cytological and genetic data indicating that Mei-41 and Grapes are components of a conserved DNA-replication/damage checkpoint pathway that triggers inhibitory phosphorylation of the Cdc2 kinase and mediates resistance to replication inhibitors and DNA-damaging agents. This pathway is nonessential during postembryonic development, but it is required to terminate the cleavage stage at the MBT. Cyclins are required for Cdc2 kinase activity, and mutations in cyclin A and cyclin B bypass the requirement for mei-41 at the MBT. These mutations do not restore wild-type syncytial cell-cycle timing or the embryonic replication checkpoint, however, suggesting that Mei-41-mediated inhibition of Cdc2 has an additional essential function at the MBT. CONCLUSIONS: The Drosophila DNA-replication/damage checkpoint pathway can be activated by externally triggered DNA damage or replication defects throughout the life cycle, and under laboratory conditions this inducible function is nonessential. During early embryogenesis, however, this pathway is activated by developmental cues and is required for the transition from maternal to zygotic control of development at the MBT.  (+info)

Modulation of drug resistance mediated by loss of mismatch repair by the DNA polymerase inhibitor aphidicolin. (5/594)

Loss of expression of mismatch repair (MMR) proteins leads to resistance of tumor cells to a variety of DNA-damaging agents, including bifunctional alkylating and monofunctional methylating agents such as cis-diaminedichloroplatinum II (CDDP) and N'-methyl-N-nitrosourea (MNU). It has been suggested that coupling to cell death does not occur in the absence of MMR, but instead, DNA lesions are bypassed during replication, giving a drug-tolerant phenotype. In the present study, we have used aphidicolin (Ap), an inhibitor of DNA polymerases, to study the role of replicative bypass in drug resistance mediated by loss of MMR. We have examined the survival of matched ovarian carcinoma cell lines with known MMR status after sequential treatment with CDDP or MNU and Ap. We show that Ap increases the sensitivity of MMR-deficient cell lines to CDDP and MNU to a greater extent than their MMR-proficient counterparts. Furthermore, loss of MMR correlates with loss of CDDP-induced G2 arrest, but this is partially restored after Ap treatment. These data support Ap sensitizing drug-resistant cancer cells that have lost MMR to CDDP and MNU and suggest that the potential use of Ap as a modulator of drug resistance should be targeted to MMR-defective tumors.  (+info)

Developmental activation of the capability to undergo checkpoint-induced apoptosis in the early zebrafish embryo. (6/594)

In this study, we demonstrate the developmental activation, in the zebrafish embryo, of a surveillance mechanism which triggers apoptosis to remove damaged cells. We determine the time course of activation of this mechanism by exposing embryos to camptothecin, an agent which specifically inhibits topoisomerase I within the DNA replication complex and which, as a consequence of this inhibition, also produces strand breaks in the genomic DNA. In response to an early (pre-gastrula) treatment with camptothecin, apoptosis is induced at a time corresponding approximately to mid-gastrula stage in controls. This apoptotic response to a block of DNA replication can also be induced by early (pre-MBT) treatment with the DNA synthesis inhibitors hydroxyurea and aphidicolin. After camptothecin treatment, a high proportion of cells in two of the embryo's three mitotic domains (the enveloping and deep cell layers), but not in the remaining domain (the yolk syncytial layer), undergoes apoptosis in a cell-autonomous fashion. The first step in this response is an arrest of the proliferation of all deep- and enveloping-layer cells. These cells continue to increase in nuclear volume and to synthesize DNA. Eventually they become apoptotic, by a stereotypic pathway which involves cell membrane blebbing, "margination" and fragmentation of nuclei, and cleavage of the genomic DNA to produce a nucleosomal ladder. Fragmentation of nuclei can be blocked by the caspase-1,4,5 inhibitor Ac-YVAD-CHO, but not by the caspase-2,3,7[, 1] inhibitor Ac-DEVD-CHO. This suggests a functional requirement for caspase-4 or caspase-5 in the apoptotic response to camptothecin. Recently, Xenopus has been shown to display a developmental activation of the capability for stress- or damaged-induced apoptosis at early gastrula stage. En masse, our experiments suggest that the apoptotic responses in zebrafish and Xenopus are fundamentally similar. Thus, as for mammals, embryos of the lower vertebrates exhibit the activation of surveillance mechanisms, early in development, to produce the selective apoptosis of damaged cells.  (+info)

Cell-cycle perturbation in Sf9 cells infected with Autographa californica nucleopolyhedrovirus. (7/594)

Flow cytometry analysis of the cell-cycle progression was performed in Sf9 cells infected with Autographa californica nucleopolyhedrovirus (AcNPV) in the cultures partially synchronized by aphidicolin exposure and deprivation. Cells infected with AcNPV during the G1 phase progressed and were arrested in the S phase in the 4 h following the infection, whereas cells infected during the S phase did not progress past the S phase. Cells infected during the G2/M phase remained in the G2/M phase without mitosis during a period of 10 h. Such cell-cycle arrest was also observed in the cells infected with ts8, a temperature-sensitive mutant of AcNPV that is defective in both genomic DNA synthesis and late gene expression. Cells with >4 N DNA content accumulated in the cultures infected with wild-type AcNPV, whereas no such cells appeared in the cultures infected with ts8, suggesting that viral origin of the DNA overaccumulated in the cells with >4 N DNA content. This was confirmed by the slot blot hybridization experiments, which showed that viral DNA, but not cellular DNA, increased strikingly in Sf9 cells during the infection with AcNPV. These results indicate that AcNPV targets at least two different checkpoints to prevent normal cell-cycle progression of Sf9 cells and that neither viral DNA replication nor expression of viral late genes is a necessary prerequisite for such AcNPV-induced cell-cycle arrest. It is suggested that the cell-cycle arrest in AcNPV-infected Sf9 cells is an event triggered early in infection by specific interaction of viral gene products with cellular components that regulate cell-cycle progression.  (+info)

Antisense oligonucleotide complementary to the BamHI-H gene family of Marek's disease virus induced growth arrest of MDCC-MSB1 cells in the S-phase. (8/594)

DNA synthesis was effectively inhibited by antisense oligonucleotide A1 complementary to the BamHI-H gene family in Marek's disease virus (MDV)-derived lymphoblastoid MDCC-MSB1 cells. When a cell cycle distribution of a total cell population was analyzed by flow cytometry, the proportion of S-phase cells increased in the cell populations by treatment with oligonucleotide A1. Approximately 60-70% of the cells appeared in the S phase for 24 and 36 hr of incubation in the presence of oligonucleotide A1 (20-30% in the untreated control cells). The inhibition of cell cycle progression by treatment with oligonucleotide A1 was reversible. When the cells were treated with 5 microM aphidicolin for 12 hr, a similar pattern of cell cycle distribution was observed to that obtained after treatment with oligonucleotide A1. Aphidicolin is an inhibitor of cellular DNA polymerase alpha, and it halts progression of the cell cycle at the G1/S border or early S phase. When the cells were treated with aphidicolin for 12 hr and subsequently incubated with oligonucleotide A1, no significant difference was observed in the cycle phase distribution of cells in the presence and absence of oligonucleotide A1. In contrast, when the cells were treated with oligonucleotide A1 for 12 hr and subsequently incubated with aphidicolin, the cell cycle did not progress from the G1/S border or early S phase to the next phase.  (+info)

Aphidicolin is an antimicrotubule agent that is specifically a inhibitor of DNA polymerase alpha. It is an antibiotic that is produced by the fungus Cephalosporium aphidicola and is used in research to study the cell cycle and DNA replication. In clinical medicine, it has been explored as a potential anticancer agent, although its use is not currently approved for this indication.

Diterpenes are a class of naturally occurring compounds that are composed of four isoprene units, which is a type of hydrocarbon. They are synthesized by a wide variety of plants and animals, and are found in many different types of organisms, including fungi, insects, and marine organisms.

Diterpenes have a variety of biological activities and are used in medicine for their therapeutic effects. Some diterpenes have anti-inflammatory, antimicrobial, and antiviral properties, and are used to treat a range of conditions, including respiratory infections, skin disorders, and cancer.

Diterpenes can be further classified into different subgroups based on their chemical structure and biological activity. Some examples of diterpenes include the phytocannabinoids found in cannabis plants, such as THC and CBD, and the paclitaxel, a diterpene found in the bark of the Pacific yew tree that is used to treat cancer.

It's important to note that while some diterpenes have therapeutic potential, others may be toxic or have adverse effects, so it is essential to use them under the guidance and supervision of a healthcare professional.

DNA Polymerase II is a type of enzyme involved in DNA replication and repair in eukaryotic cells. It plays a crucial role in the process of proofreading and correcting errors that may occur during DNA synthesis.

During DNA replication, DNA polymerase II helps to fill in gaps or missing nucleotides behind the main replicative enzyme, DNA Polymerase epsilon. It also plays a significant role in repairing damaged DNA by removing and replacing incorrect or damaged nucleotides.

DNA Polymerase II is highly accurate and has a strong proofreading activity, which allows it to correct most of the errors that occur during DNA synthesis. This enzyme is also involved in the process of translesion synthesis, where it helps to bypass lesions or damage in the DNA template, allowing replication to continue.

Overall, DNA Polymerase II is an essential enzyme for maintaining genomic stability and preventing the accumulation of mutations in eukaryotic cells.

DNA replication is the biological process by which DNA makes an identical copy of itself during cell division. It is a fundamental mechanism that allows genetic information to be passed down from one generation of cells to the next. During DNA replication, each strand of the double helix serves as a template for the synthesis of a new complementary strand. This results in the creation of two identical DNA molecules. The enzymes responsible for DNA replication include helicase, which unwinds the double helix, and polymerase, which adds nucleotides to the growing strands.

DNA-directed DNA polymerase is a type of enzyme that synthesizes new strands of DNA by adding nucleotides to an existing DNA template in a 5' to 3' direction. These enzymes are essential for DNA replication, repair, and recombination. They require a single-stranded DNA template, a primer with a free 3' hydroxyl group, and the four deoxyribonucleoside triphosphates (dNTPs) as substrates to carry out the polymerization reaction.

DNA polymerases also have proofreading activity, which allows them to correct errors that occur during DNA replication by removing mismatched nucleotides and replacing them with the correct ones. This helps ensure the fidelity of the genetic information passed from one generation to the next.

There are several different types of DNA polymerases, each with specific functions and characteristics. For example, DNA polymerase I is involved in both DNA replication and repair, while DNA polymerase III is the primary enzyme responsible for DNA replication in bacteria. In eukaryotic cells, DNA polymerase alpha, beta, gamma, delta, and epsilon have distinct roles in DNA replication, repair, and maintenance.

Chromosome fragile sites are specific locations along the length of a chromosome that are prone to breakage or rearrangement when exposed to certain chemicals or conditions, such as replication stress during cell division. These sites are often characterized by the presence of repetitive DNA sequences and proteins that help maintain the stability of the chromosome.

Fragile sites can be classified into two categories: common and rare. Common fragile sites are present in most individuals and are typically not associated with genetic disorders, while rare fragile sites are less common and may be linked to specific genetic conditions or increased risk for cancer.

When a chromosome breaks at a fragile site, it can lead to various genetic abnormalities such as deletions, duplications, inversions, or translocations of genetic material. These changes can have significant consequences on gene expression and function, potentially leading to developmental disorders, intellectual disability, cancer, or other health issues.

It is important to note that not all fragile sites will result in genetic abnormalities, as some may remain stable under normal conditions. However, certain factors such as environmental exposures, aging, or inherited genetic predispositions can increase the likelihood of chromosomal instability at fragile sites.

Chromosome fragility refers to the susceptibility of specific regions on chromosomes to break or become unstable during cell division. These fragile sites are prone to forming gaps or breaks in the chromosome structure, which can lead to genetic rearrangements, including deletions, duplications, or translocations.

Chromosome fragility is often associated with certain genetic disorders and syndromes. For example, the most common fragile site in human chromosomes is FRAXA, located on the X chromosome, which is linked to Fragile X Syndrome, a leading cause of inherited intellectual disability and autism.

Environmental factors such as exposure to chemicals or radiation can also increase chromosome fragility, leading to an increased risk of genetic mutations and diseases.

Mimosine is not a medical term per se, but it is a chemical compound that has been studied in the context of biomedical research. Mimosine is an alkaloid found in certain plants, including the mimosa tree (Leucaena leucocephala). It has been shown to have various biological activities, such as anti-proliferative and cytotoxic effects on certain types of cells. However, it is not a term that is commonly used in medical diagnoses or treatments.

In terms of its chemical structure, mimosine is an amino acid that contains a pyrrolidone ring with a hydroxyl group at the 3-position and a carboxylic acid group at the 2-position. It can inhibit certain enzymes involved in DNA replication and repair, which may contribute to its anti-proliferative effects.

It's worth noting that mimosine has been studied for its potential therapeutic benefits, such as its ability to inhibit the growth of cancer cells. However, more research is needed to determine its safety and efficacy in humans before it can be considered a viable treatment option.

Phosphonoacetic acid (PAA) is not a naturally occurring substance, but rather a synthetic compound that is used in medical and scientific research. It is a colorless, crystalline solid that is soluble in water.

In a medical context, PAA is an inhibitor of certain enzymes that are involved in the replication of viruses, including HIV. It works by binding to the active site of these enzymes and preventing them from carrying out their normal functions. As a result, PAA has been studied as a potential antiviral agent, although it is not currently used as a medication.

It's important to note that while PAA has shown promise in laboratory studies, its safety and efficacy have not been established in clinical trials, and it is not approved for use as a drug by regulatory agencies such as the U.S. Food and Drug Administration (FDA).

Hydroxyurea is an antimetabolite drug that is primarily used in the treatment of myeloproliferative disorders such as chronic myelogenous leukemia (CML), essential thrombocythemia, and polycythemia vera. It works by interfering with the synthesis of DNA, which inhibits the growth of cancer cells.

In addition to its use in cancer therapy, hydroxyurea is also used off-label for the management of sickle cell disease. In this context, it helps to reduce the frequency and severity of painful vaso-occlusive crises by increasing the production of fetal hemoglobin (HbF), which decreases the formation of sickled red blood cells.

The medical definition of hydroxyurea is:

A hydantoin derivative and antimetabolite that inhibits ribonucleoside diphosphate reductase, thereby interfering with DNA synthesis. It has been used as an antineoplastic agent, particularly in the treatment of myeloproliferative disorders, and more recently for the management of sickle cell disease to reduce the frequency and severity of painful vaso-occlusive crises by increasing fetal hemoglobin production.

DNA Polymerase I is a type of enzyme that plays a crucial role in DNA replication and repair in prokaryotic cells, such as bacteria. It is responsible for synthesizing new strands of DNA by adding nucleotides to the 3' end of an existing strand, using the complementary strand as a template.

DNA Polymerase I has several key functions during DNA replication:

1. **5' to 3' exonuclease activity:** It can remove nucleotides from the 5' end of a DNA strand in a process called excision repair, which helps to correct errors that may have occurred during DNA replication.
2. **3' to 5' exonuclease activity:** This enzyme can also proofread newly synthesized DNA by removing incorrect nucleotides from the 3' end of a strand, ensuring accurate replication.
3. **Polymerase activity:** DNA Polymerase I adds new nucleotides to the 3' end of an existing strand, extending the length of the DNA molecule during replication and repair processes.
4. **Pyrophosphorolysis:** It can reverse the polymerization reaction by removing a nucleotide from the 3' end of a DNA strand while releasing pyrophosphate, which is an important step in some DNA repair pathways.

In summary, DNA Polymerase I is a versatile enzyme involved in various aspects of DNA replication and repair, contributing to the maintenance of genetic information in prokaryotic cells.

Deoxyribonucleotides are the building blocks of DNA (deoxyribonucleic acid). They consist of a deoxyribose sugar, a phosphate group, and one of four nitrogenous bases: adenine (A), guanine (G), cytosine (C), or thymine (T). A deoxyribonucleotide is formed when a nucleotide loses a hydroxyl group from its sugar molecule. In DNA, deoxyribonucleotides link together to form a long, double-helix structure through phosphodiester bonds between the sugar of one deoxyribonucleotide and the phosphate group of another. The sequence of these nucleotides carries genetic information that is essential for the development and function of all known living organisms and many viruses.

Nucleic acid synthesis inhibitors are a class of antimicrobial, antiviral, or antitumor agents that block the synthesis of nucleic acids (DNA or RNA) by interfering with enzymes involved in their replication. These drugs can target various stages of nucleic acid synthesis, including DNA transcription, replication, and repair, as well as RNA transcription and processing.

Examples of nucleic acid synthesis inhibitors include:

1. Antibiotics like quinolones (e.g., ciprofloxacin), rifamycins (e.g., rifampin), and trimethoprim, which target bacterial DNA gyrase, RNA polymerase, or dihydrofolate reductase, respectively.
2. Antiviral drugs like reverse transcriptase inhibitors (e.g., zidovudine, lamivudine) and integrase strand transfer inhibitors (e.g., raltegravir), which target HIV replication by interfering with viral enzymes required for DNA synthesis.
3. Antitumor drugs like antimetabolites (e.g., methotrexate, 5-fluorouracil) and topoisomerase inhibitors (e.g., etoposide, doxorubicin), which interfere with DNA replication and repair in cancer cells.

These drugs have been widely used for treating various bacterial and viral infections, as well as cancers, due to their ability to selectively inhibit the growth of target cells without affecting normal cellular functions significantly. However, they may also cause side effects related to their mechanism of action or off-target effects on non-target cells.

The cell cycle is a series of events that take place in a cell leading to its division and duplication. It consists of four main phases: G1 phase, S phase, G2 phase, and M phase.

During the G1 phase, the cell grows in size and synthesizes mRNA and proteins in preparation for DNA replication. In the S phase, the cell's DNA is copied, resulting in two complete sets of chromosomes. During the G2 phase, the cell continues to grow and produces more proteins and organelles necessary for cell division.

The M phase is the final stage of the cell cycle and consists of mitosis (nuclear division) and cytokinesis (cytoplasmic division). Mitosis results in two genetically identical daughter nuclei, while cytokinesis divides the cytoplasm and creates two separate daughter cells.

The cell cycle is regulated by various checkpoints that ensure the proper completion of each phase before progressing to the next. These checkpoints help prevent errors in DNA replication and division, which can lead to mutations and cancer.

In the context of cell biology, "S phase" refers to the part of the cell cycle during which DNA replication occurs. The "S" stands for synthesis, reflecting the active DNA synthesis that takes place during this phase. It is preceded by G1 phase (gap 1) and followed by G2 phase (gap 2), with mitosis (M phase) being the final stage of the cell cycle.

During S phase, the cell's DNA content effectively doubles as each chromosome is replicated to ensure that the two resulting daughter cells will have the same genetic material as the parent cell. This process is carefully regulated and coordinated with other events in the cell cycle to maintain genomic stability.

Desmosterol is a sterol, which is a type of lipid molecule similar to cholesterol. It is an intermediate in the biosynthetic pathway that leads to the production of cholesterol in the body. Specifically, desmosterol is produced from 7-dehydrocholesterol and is then converted to cholesterol through a series of additional steps.

Desmosterol is found in small amounts in various tissues throughout the body, including the brain, where it plays important roles in maintaining cell membrane structure and function. However, abnormal accumulations of desmosterol have been associated with certain genetic disorders, such as desmosterolosis and lathosterolosis, which are characterized by developmental delays, cataracts, and other neurological symptoms.

It's worth noting that while desmosterol is an important molecule in the body, it is not typically measured or monitored in a clinical setting unless there is a specific reason to suspect a problem with its metabolism.

Deoxycytosine nucleotides are chemical compounds that are the building blocks of DNA, one of the two nucleic acids found in cells. Specifically, deoxycytosine nucleotides consist of a deoxyribose sugar, a phosphate group, and the nitrogenous base cytosine.

In DNA, deoxycytosine nucleotides pair with deoxyguanosine nucleotides through hydrogen bonding between the bases to form a stable structure that stores genetic information. The synthesis of deoxycytosine nucleotides is tightly regulated in cells to ensure proper replication and repair of DNA.

Disruptions in the regulation of deoxycytosine nucleotide metabolism can lead to various genetic disorders, including mitochondrial DNA depletion syndromes and cancer. Therefore, understanding the biochemistry and regulation of deoxycytosine nucleotides is crucial for developing effective therapies for these conditions.

DNA Polymerase III is a critical enzyme in the process of DNA replication in bacteria. It is responsible for synthesizing new strands of DNA by adding nucleotides to the growing chain, based on the template provided by the existing DNA strand. This enzyme has multiple subunits and possesses both polymerase and exonuclease activities. The polymerase activity adds nucleotides to the growing DNA strand, while the exonuclease activity proofreads and corrects any errors that occur during replication. Overall, DNA Polymerase III plays a crucial role in maintaining the accuracy and integrity of genetic information during bacterial cell division.

Deoxyribonucleic acid (DNA) is the genetic material present in the cells of organisms where it is responsible for the storage and transmission of hereditary information. DNA is a long molecule that consists of two strands coiled together to form a double helix. Each strand is made up of a series of four nucleotide bases - adenine (A), guanine (G), cytosine (C), and thymine (T) - that are linked together by phosphate and sugar groups. The sequence of these bases along the length of the molecule encodes genetic information, with A always pairing with T and C always pairing with G. This base-pairing allows for the replication and transcription of DNA, which are essential processes in the functioning and reproduction of all living organisms.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

Formazans are colored compounds produced during certain chemical reactions, such as the reduction of tetrazolium salts. These compounds have a characteristic deep red or purple color and are often used as an indicator of metabolic activity in biological systems, including cells and microorganisms. In medical research and diagnostics, formazans are sometimes used to measure cell viability, enzyme activity, and other physiological processes. However, it's important to note that 'formazans' is not a medical term per se, but rather a chemical term with applications in the medical field.

Deoxyguanine nucleotides are chemical compounds that are the building blocks of DNA, one of the fundamental molecules of life. Specifically, deoxyguanine nucleotides contain a sugar molecule called deoxyribose, a phosphate group, and the nitrogenous base guanine.

Guanine is one of the four nitrogenous bases found in DNA, along with adenine, thymine, and cytosine. In DNA, guanine always pairs with cytosine through hydrogen bonding, forming a stable base pair that is crucial for maintaining the structure and integrity of the genetic code.

Deoxyguanine nucleotides are synthesized in cells during the process of DNA replication, which occurs prior to cell division. During replication, the double helix structure of DNA is unwound, and each strand serves as a template for the synthesis of a new complementary strand. Deoxyguanine nucleotides are added to the growing chain of nucleotides by an enzyme called DNA polymerase, which catalyzes the formation of a phosphodiester bond between the deoxyribose sugar of one nucleotide and the phosphate group of the next.

Abnormalities in the synthesis or metabolism of deoxyguanine nucleotides can lead to genetic disorders and cancer. For example, mutations in genes that encode enzymes involved in the synthesis of deoxyguanine nucleotides have been linked to inherited diseases such as xeroderma pigmentosum and Bloom syndrome, which are characterized by increased sensitivity to sunlight and a predisposition to cancer. Additionally, defects in the repair of damaged deoxyguanine nucleotides can lead to the accumulation of mutations and contribute to the development of cancer.

Parvoviridae is a family of small, non-enveloped viruses that infect a wide range of hosts, including humans, animals, and birds. These viruses have a single-stranded DNA genome and replicate in the nucleus of infected cells. They are resistant to heat, acid, and organic solvents, making them difficult to inactivate.

The family Parvoviridae is divided into two subfamilies: Parvovirinae and Densovirinae. Parvovirinae infect vertebrates, while Densovirinae infect invertebrates. The subfamily Parvovirinae includes several genera that infect various hosts, such as humans, dogs, cats, and primates.

Parvovirus B19 is a well-known member of this family that causes a variety of clinical manifestations in humans, including fifth disease (slapped cheek syndrome), arthralgia, and occasionally more severe diseases in immunocompromised individuals or those with certain hematological disorders.

In animals, parvoviruses can cause serious diseases such as canine parvovirus infection in dogs and feline panleukopenia in cats, which can be fatal if left untreated.

The cell nucleus is a membrane-bound organelle found in the eukaryotic cells (cells with a true nucleus). It contains most of the cell's genetic material, organized as DNA molecules in complex with proteins, RNA molecules, and histones to form chromosomes.

The primary function of the cell nucleus is to regulate and control the activities of the cell, including growth, metabolism, protein synthesis, and reproduction. It also plays a crucial role in the process of mitosis (cell division) by separating and protecting the genetic material during this process. The nuclear membrane, or nuclear envelope, surrounding the nucleus is composed of two lipid bilayers with numerous pores that allow for the selective transport of molecules between the nucleoplasm (nucleus interior) and the cytoplasm (cell exterior).

The cell nucleus is a vital structure in eukaryotic cells, and its dysfunction can lead to various diseases, including cancer and genetic disorders.

Viral DNA refers to the genetic material present in viruses that consist of DNA as their core component. Deoxyribonucleic acid (DNA) is one of the two types of nucleic acids that are responsible for storing and transmitting genetic information in living organisms. Viruses are infectious agents much smaller than bacteria that can only replicate inside the cells of other organisms, called hosts.

Viral DNA can be double-stranded (dsDNA) or single-stranded (ssDNA), depending on the type of virus. Double-stranded DNA viruses have a genome made up of two complementary strands of DNA, while single-stranded DNA viruses contain only one strand of DNA.

Examples of dsDNA viruses include Adenoviruses, Herpesviruses, and Poxviruses, while ssDNA viruses include Parvoviruses and Circoviruses. Viral DNA plays a crucial role in the replication cycle of the virus, encoding for various proteins necessary for its multiplication and survival within the host cell.

Antiviral agents are a class of medications that are designed to treat infections caused by viruses. Unlike antibiotics, which target bacteria, antiviral agents interfere with the replication and infection mechanisms of viruses, either by inhibiting their ability to replicate or by modulating the host's immune response to the virus.

Antiviral agents are used to treat a variety of viral infections, including influenza, herpes simplex virus (HSV) infections, human immunodeficiency virus (HIV) infection, hepatitis B and C, and respiratory syncytial virus (RSV) infections.

These medications can be administered orally, intravenously, or topically, depending on the type of viral infection being treated. Some antiviral agents are also used for prophylaxis, or prevention, of certain viral infections.

It is important to note that antiviral agents are not effective against all types of viruses and may have significant side effects. Therefore, it is essential to consult with a healthcare professional before starting any antiviral therapy.

Simian Virus 40 (SV40) is a polyomavirus that is found in both monkeys and humans. It is a DNA virus that has been extensively studied in laboratory settings due to its ability to transform cells and cause tumors in animals. In fact, SV40 was discovered as a contaminant of poliovirus vaccines that were prepared using rhesus monkey kidney cells in the 1950s and 1960s.

SV40 is not typically associated with human disease, but there has been some concern that exposure to the virus through contaminated vaccines or other means could increase the risk of certain types of cancer, such as mesothelioma and brain tumors. However, most studies have failed to find a consistent link between SV40 infection and cancer in humans.

The medical community generally agrees that SV40 is not a significant public health threat, but researchers continue to study the virus to better understand its biology and potential impact on human health.

HeLa cells are a type of immortalized cell line used in scientific research. They are derived from a cancer that developed in the cervical tissue of Henrietta Lacks, an African-American woman, in 1951. After her death, cells taken from her tumor were found to be capable of continuous division and growth in a laboratory setting, making them an invaluable resource for medical research.

HeLa cells have been used in a wide range of scientific studies, including research on cancer, viruses, genetics, and drug development. They were the first human cell line to be successfully cloned and are able to grow rapidly in culture, doubling their population every 20-24 hours. This has made them an essential tool for many areas of biomedical research.

It is important to note that while HeLa cells have been instrumental in numerous scientific breakthroughs, the story of their origin raises ethical questions about informed consent and the use of human tissue in research.

DNA damage refers to any alteration in the structure or composition of deoxyribonucleic acid (DNA), which is the genetic material present in cells. DNA damage can result from various internal and external factors, including environmental exposures such as ultraviolet radiation, tobacco smoke, and certain chemicals, as well as normal cellular processes such as replication and oxidative metabolism.

Examples of DNA damage include base modifications, base deletions or insertions, single-strand breaks, double-strand breaks, and crosslinks between the two strands of the DNA helix. These types of damage can lead to mutations, genomic instability, and chromosomal aberrations, which can contribute to the development of diseases such as cancer, neurodegenerative disorders, and aging-related conditions.

The body has several mechanisms for repairing DNA damage, including base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair. However, if the damage is too extensive or the repair mechanisms are impaired, the cell may undergo apoptosis (programmed cell death) to prevent the propagation of potentially harmful mutations.

ISBN 978-0-12-465327-6. DeFilippes, FM (Nov 1984). "Effect of aphidicolin on vaccinia virus: isolation of an aphidicolin- ... Aphidicolin is a reversible inhibitor of eukaryotic nuclear DNA replication. It blocks the cell cycle at early S phase. It is a ... Aphidicolin product page Archived June 26, 2006, at the Wayback Machine from Fermentek v t e (Webarchive template wayback links ... Natural aphidicolin is a secondary metabolite of the fungus Nigrospora oryzae. Dhillon VS, Husain SA, Ray GN (2003). " ...
Robert Ireland's synthesis of (±)-aphidicolin uses the Wolff rearrangement to do a tandem ring-contraction, and [2 + 2] ... aphidicolin and (.+-.)-.beta.-chamigrene". J. Org. Chem. 49 (6): 1001-1013. doi:10.1021/jo00180a010.{{cite journal}}: CS1 maint ...
Trost, B. M.; Nishimura, Yoshio; Yamamoto, Kagetoshi (1979). "A Total Synthesis of Aphidicolin". J. Am. Chem. Soc. 101 (5): ... In 1979 Trost reported the synthesis of Aphidicolin using methodology around the vinylcyclopropane rearrangement developed in ...
Aphidicolin is a mycotoxin originally known to be produced by the fungus, Cephalosporium aphidicola. This antiviral compound ... Starratt, A. N.; Loschiavo, S. R. (March 1974). "The production of aphidicolin by Nigrospora sphaerica". Canadian Journal of ...
McMurry, J. E.; Andrus A.; Ksander G. M.; Muesser, J. H.; Johnson, M. A. "Stereospecific Total Synthesis of Aphidicolin.". ...
Murano I, Kuwano A, Kajii T (August 1989). "Fibroblast-specific common fragile sites induced by aphidicolin". Human Genetics. ...
Aphidicolin is an antibiotic isolated from the fungus Cephalosporum aphidicola. It is a reversible inhibitor of eukaryotic ... "Structural basis for inhibition of DNA replication by aphidicolin". Nucleic Acids Research. 42 (22): 14013-21. doi:10.1093/nar/ ...
Nagano, H; Ikegami, S (November 1980). "Aphidicolin: a specific inhibitor of eukaryotic DNA polymerase alpha". Seikagaku: The ...
Fragile site, aphidicolin type, common, fra(3)(p24.2) is a protein that in humans is encoded by the FRA3A gene. "Human PubMed ... "Entrez Gene: Fragile site, aphidicolin type, common, fra(3)(p24.2)". Retrieved 2014-08-05. v t e (Articles with short ...
... aphidicolin, terretonin, and andrastin A by plasmid insertion; paxilline and aflatrem by co-transformation; and aspyridone, ...
Sensitivity to novobiocin, bacitracin, anisomycin, aphidicolin, and rifampicin have been observed. However, no sensitivity has ...
"Isolation and Characterization of Aphidicolin and Chlamydosporol Derivatives from Tolypocladium inflatum". Journal of Natural ...
They used aphidicolin (APH) to inhibit DNA polymerase and prevent DNA replication. When treated with Cyclin B in interphase, ...
The chemical agent aphidicolin can be added to easily and effectively synchronize chloroplast division. The peroxisome division ... of chloroplast division in the ultramicro-alga Cyanidioschyzon merolae by treatment with both light and aphidicolin". J. Phycol ...
"Effects of monocerin on cell cycle progression in maize root meristems synchronized with aphidicolin". Plant Cell Reports. 15 ( ...
"FRAXD fragile site, aphidicolin type, common, fra(X)(q27.2) D [Homo sapiens (human)] - Gene - NCBI". " ... FRAXD or FRAXD gene is a gene symbol for fragile site, aphidicolin type, common, fra(X)(q27.2) D. The locus of the gene is ...
The majority of breakages at CFSs are induced by low doses of the antibiotic aphidicolin (APH). Co-treatment with low ... Glover, TW; Berger, C; Coyle, J; Echo, B (1984). "DNA polymerase alpha inhibition by aphidicolin induces gaps and breaks at ...
3-deoxyaphidicolin and aphidicolin-17-monoacetate". Nucleic Acids Research. 11 (4): 1197-209. doi:10.1093/nar/11.4.1197. PMC ...
3-deoxyaphidicolin and aphidicolin-17-monoacetate". Nucleic Acids Res. 11 (4): 1197-2000. doi:10.1093/nar/11.4.1197. PMC 325786 ...
3-deoxyaphidicolin and aphidicolin-17-monoacetate". Nucleic Acids Res. 11 (4): 1197-2000. doi:10.1093/nar/11.4.1197. PMC 325786 ...
"Cloning of a gene cluster responsible for the biosynthesis of diterpene aphidicolin, a specific inhibitor of DNA polymerase α ... a key enzyme responsible for formation of an unusual diterpene skeleton in biosynthesis of aphidicolin". Journal of the ...
In the presence of DNA damage or replication stress (UV light, methyl methanesulfonate, hydroxyurea or aphidicolin), the POLD4/ ...
Further studies to support the theory of cell-proliferation were done by introducing then removing the drug aphidicolin which ...
Subsequent discoveries included alamethicin, aphidicolin, brefeldin A, cephalosporin, cerulenin, citromycin, eupenifeldin, ...
... or aphidicolin, each of which had been documented to exert its effects in a particular phase of the cell cycle. Surprisingly, ...
He and his students published syntheses of 2-deoxyribose, aaptamine, aphidicolin, apiose, arachidonic acid, arcyriaflavin B, ...
... aphidicolin type, common, fra(3)(p24.2) FRMD4B encoding protein FERM domain containing 4B GHRLOS: non-coding RNA ghrelin ...
Aphidicolin Experimental drugs and drug precursors: Parthenolide, Puromycin, Rapamycin, Anisomycin, Thapsigargin, cyclopamine, ...
... aphidicolin MeSH D02.455.849.291.162 - atractyloside MeSH D02.455.849.291.206 - diterpenes, abietane MeSH D02.455.849.291.228 ...
Most notable are prostaglandin F2α, narwedine, aphidicolin, taxusin, Taxol and hemibrevetoxin B. Dr. Holton also serves as ...
ISBN 978-0-12-465327-6. DeFilippes, FM (Nov 1984). "Effect of aphidicolin on vaccinia virus: isolation of an aphidicolin- ... Aphidicolin is a reversible inhibitor of eukaryotic nuclear DNA replication. It blocks the cell cycle at early S phase. It is a ... Aphidicolin product page Archived June 26, 2006, at the Wayback Machine from Fermentek v t e (Webarchive template wayback links ... Natural aphidicolin is a secondary metabolite of the fungus Nigrospora oryzae. Dhillon VS, Husain SA, Ray GN (2003). " ...
Aphidicolin, Ready Made Solution. Empirical Formula (Hill Notation). : C20H34O4. CAS No.. : 38966-21-1. Molecular Weight. : ...
Note: Aphidicolin, WTC PM and olaparib are present during IdU pulse. (g-i) Top; Locus map of SbfI digested R2 segment. Bottom; ... Note: Aphidicolin, WTC PM and olaparib are present during IdU pulse. (f) Replication fork speed during the IdU pulse of SMARD ( ... Note: Aphidicolin, WTC-PM and Olaparib are present during IdU pulse. (k) Replication fork speed during the IdU pulse of SMARD ( ... Note: Aphidicolin, WTC-PM and Olaparib are present during IdU pulse. (f): Replication fork speed during the IdU pulse of SMARD ...
... aphidicolin (Tiwari et al., 2008), picrotoxin (López-Martín et al., 2009), doxorubicin (Zhijian et al., 2010), and incoherent ...
Structural basis for inhibition of DNA replication by aphidicolin. Nucleic Acids Res. 2014 Dec 16. 42 (22):14013-21. [QxMD ...
Structural basis for inhibition of DNA replication by aphidicolin. Nucleic Acids Res. 2014 Dec 16. 42 (22):14013-21. [QxMD ...
Phosphonoacetic Acid: A simple organophosphorus compound that inhibits DNA polymerase, especially in viruses and is used as an antiviral agent.
For aphidicolin treatment, cells were incubated with 0.3 μM aphidicolin for 24 hours. The drug was removed by washing the cells ... and without aphidicolin (an inhibitor of DNA replication) pretreatment (Figure 4C). In the absence of aphidicolin treatment, ... Treatment with aphidicolin amplified this phenotype (Figure 4C and Supplemental Figure 2C). Thus, MCM4 mutation affects DNA ... Breakage analysis. Primary or SV40 fibroblasts were treated with 0.3 μM aphidicolin for 24 hours, arrested by incubation with ...
B Representative image of γH2AX immunostaining in MCF7 cells treated with 1 µM xentuzumab or 0.3 µM aphidicolin for 72 h. Scale ... 1B). The foci were comparable in size and intensity to foci induced by aphidicolin that causes replication stress by inhibiting ... MK-1775 from Axon Medchem and aphidicolin from Sigma-Aldrich. ...
Obtainment of aphidicolin and enhydrin derivatives through biotransformation and.... Natural and Synthetic Products ...
Aphidicolin. 1 mg. 156.22 €. -. Toku-e. A104. Apicidin. 2 mg. 178.69 €. -. Toku-e. ...
Preparation of Androstanes Related to Aphidicolin. 2007, Vol. 72, Issue 11, pp. 1545-1552 [Abstract] ...
Aphidicolin. $146.00. - $511.00. exc GST Code: BIA-A1217. CAS #: 38966-21-1. Molecular Formula: C20H34O4. Molecular Weight: ...
The nuclear translocation of p100prp1/zer1/prp6 was not prevented by treatment of 1-cell embryos with aphidicolin, indicating ...
... and quantify replication fork stalling by replication inhibitor aphidicolin. These data demonstrate the potential for cell free ...
After 24 h, the cells were treated with aphidicolin and EGFP fluorescence for both setups was followed in real-time 24 h later ... After 6 h, the transfection medium was replaced with fresh medium and in one set of experiments aphidicolin was added after 24 ... B) Expression of EGFP-NBPF1 in cells stimulated with aphidicolin showed increased accumulation in the form of particulate or ... Doxorubicine hydrochloride (Doxo; Sigma) was used at a final concentration of 350 nM during 24 h. Aphidicolin (Sigma) was used ...
A Comprehensive Analysis of the Dynamic Response to Aphidicolin-Mediated Replication Stress Uncovers Targets for ATM and ATMIN ...
Aphidicolin 14.02206 11.91168 ATM kinase inhibitor 70.42186 83.20541 ATM/ATR kinase inhibitor 59.07151 76.76988 Aurora kinase ...
2 days in vitro (DIV). As 13% of astrocytes divided every 2 days (see Figure S1A available online and see below), aphidicolin, ... serum-free base media with 0.5 μg/ml of aphidicolin to inhibit cell division and assessed the ability of individual growth ...
Niechi, I., Erices, J. I., Carrillo-Beltrán, D., Uribe-Ojeda, A., Torres, Á., Rocha, J. D., Uribe, D., Toro, M. A., Villalobos-Nova, K., Gaete-Ramírez, B., Mingo, G., Owen, G. I., Varas-Godoy, M., Jara, L., Aguayo, F., Burzio, V. A., Quezada-Monrás, C. & Tapia, J. C., Feb 2023, In: Cells. 12, 3, 506.. Research output: Contribution to journal › Article › peer-review ...
Dive into the research topics of Involvement of DNA replication in ultraviolet-induced apoptosis of mammalian cells. Together they form a unique fingerprint. ...
Dive into the research topics of Chinese hamster ovary cell mutants resistant to DNA polymerase inhibitors - I. Isolation and biochemical genetic characterization. Together they form a unique fingerprint. ...
Here, we contrasted the genomic landscape of cytogenetically defined aphidicolin-induced CFSs (aCFSs) to that of nonfragile ... Here, we contrasted the genomic landscape of cytogenetically defined aphidicolin-induced CFSs (aCFSs) to that of nonfragile ... Here, we contrasted the genomic landscape of cytogenetically defined aphidicolin-induced CFSs (aCFSs) to that of nonfragile ... Here, we contrasted the genomic landscape of cytogenetically defined aphidicolin-induced CFSs (aCFSs) to that of nonfragile ...
... increase in subtelomeric replication initiation when replication fork progression from the telomere was hindered by aphidicolin ...
This graph shows the total number of publications written about "Diterpenes, Abietane" by people in Harvard Catalyst Profiles by year, and whether "Diterpenes, Abietane" was a major or minor topic of these publication ...
... in primary neural stem/progenitor cells undergoing aphidicolin-induced, mild replication stress to assess the potential ...
Mild replication stress was induced with the DNA-polymerase inhibitor aphidicolin (APH). Fibroblasts from patients with the DNA ...
1. H2O2 alone; 2. H2O2 plus aphidicolin; 3. MK for 1 h prior to H2O2; 4. MK and aphidicolin for 1 h prior to and 30 min after H ... MK and aphidicolin were present during the post-H2O2 incubations where indicated. C. Aphidicolin suppresses niraparibs ... 1. Untreated control; 2. MK alone; 3. Aphidicolin alone; 4. MK + aphidicolin; 5. 5 Gy alone analyzed 4 h after irradiation; 6. ... MK and aphidicolin for 1 h prior to H2O2 and analyzed 30 min after H2O2; 6. Aphidicolin for 1 h prior to H2O2 and analyzed 30 ...
treated for 24 hours with 2μg/mL aphidicolin +3 hour 10nm DHT Permissive Robust Homo sapiens. GSE82202 ... MA0007.3 ... 2μg/mL aphidicolin for 15 hours, followed by washout and treatment with 50ng/mL nocodozole for 9 hours +3 hour 10nm DHT ...
  • Aphidicolin is a reversible inhibitor of eukaryotic nuclear DNA replication. (
  • Here we find that the replication fork progresses at 1.3kbp/min in mouse fibroblast cells, consistent with other studies, and quantify replication fork stalling by replication inhibitor aphidicolin. (
  • Treatments with a DNA synthesis inhibitor, aphidicolin, show that the number of nuclear divisions, and perhaps the DNA to cytoplasmic ratio, are critical for the appearance of lineage-specific differentiation.Conclusion: Our work corroborates previous studies demonstrating that the cleavage program is causally involved in the spatial segregation and/or activation of factors that give rise to distinct cell types in ctenophore development. (
  • The adozelesin-induced RPA hyperphosphorylation can be blocked by the replicative DNA polymerase inhibitor, aphidicolin, overwatch 2 aimbot hack download that adozelesin-triggered cellular DNA damage responses require active DNA replication forks. (
  • Here, we contrasted the genomic landscape of cytogenetically defined aphidicolin-induced CFSs (aCFSs) to that of nonfragile sites, using multiple logistic regression. (
  • Finally, the multi-Ub conjugates of TOP1 were observed whether or not aphidicolin was included in cotreatment with CPT, indicating that replication fork activity was not involved in making TOP1 a substrate for ubiquitination. (
  • Regulatory effect of aphidicolin on the activity of DNA polymerase alpha from mouse myeloma. (
  • Natural aphidicolin is a secondary metabolite of the fungus Nigrospora oryzae. (
  • Aphidicolin increased CREB activity and ectopic expression of dominantnegative inhibitor of CREB, A-CREB, repressed the stimulatory effects of aphidicolin on eNOS gene expression and its promoter activity. (
  • Aphidicolin increased p-ATM-Ser 1981 and the knockdown of ATM using siRNA attenuated all stimulatory effects of aphidicolin on p-Akt-Ser 473 , p-CREB-Ser 133 , eNOS expression, and NO production. (
  • Additionally, these stimulatory effects of aphidicolin were similarly observed in human umbilical vein endothelial cells. (
  • Common fragile sites (CFSs) are found widely distributed in the population, with the largest subset of these sites being induced by aphidicolin (APH). (
  • Reference: DNA polymerase alpha inhibition by aphidicolin induces gaps and breaks at common fragile sites in human chromosomes. (
  • The fragile X site, which can also be induced by thymidylate stress, was not induced by aphidicolin in lymphocytes, suggesting a separate mechanism for its induction. (
  • The hot spots induced by aphidicolin represent a new class of fragile sites which we term common fragile sites. (
  • 5. Determination of the specificity of aphidicolin-induced breakage of the human 3p14.2 fragile site. (
  • Aphidicolin represents a novel tool for detection of hot spots on human chromosomes through the mechanism of DNA polymerase alpha inhibition. (
  • In contrast, aphidicolin, which blocks cell growth through inhibition of DNA polymerase alpha, has no effect on the DHFR promoter. (
  • Mutally exclusive inhibition of herpesvirus DNA polymerase by aphidicolin, phosphonoformate, and acyclic nucleoside triphosphate. (
  • The frequency of R-loop-dependent fork stalling events is also increased after TIMELESS depletion or a partial inhibition of replicative DNA polymerases by aphidicolin, suggesting that this phenomenon is due to a global replication slowdown. (
  • Here we report that low doses of hydroxyurea, an inhibitor of ribonucleotide reductase and an important drug in the treatment of sickle cell disease and other diseases induces a high frequency of de novo CNVs in cultured human cells that resemble pathogenic and aphidicolin-induced CNVs in size and breakpoint structure. (
  • Aphidicolin is a reversible inhibitor of eukaryotic nuclear DNA replication. (
  • We demonstrate that these proteins associate with chromatin and are phosphorylated when replication is inhibited by aphidicolin. (
  • We further demonstrate that XRad17 is essential for the chromatin binding and checkpoint-dependent phosphorylation of X9-1-1 and for the activation of XChk1 when the replication checkpoint is induced by aphidicolin. (
  • 1. A 350-kb cosmid contig in 3p14.2 that crosses the t(3;8) hereditary renal cell carcinoma translocation breakpoint and 17 aphidicolin-induced FRA3B breakpoints. (
  • Following exposure to aphidicolin, double-strand breaks were not correctly repaired in cells expressing mtRpa1. (
  • Using a genotoxic agent aphidicolin, we investigated how DDRs regulate NO production in bovine aortic endothelial cells. (
  • In conclusion, our results demonstrate that in response to aphidicolin, activation of ATM/Akt/CREB/eNOS signaling cascade mediates increase of NO production and vessel relaxation in endothelial cells and rat aortas. (
  • To generate mature RPE monolayers, we induced primary cilium in committed RPE cells using known cilia inducers like aphidicolin and PGE2. (
  • Targeting DNA repair with aphidicolin sensitizes primary chronic lymphocytic leukemia cells to purine analogs. (
  • Here we describe a protocol to identify at genome wide and at high resolution the genomic sites where MiDAS occurs in cells exposed to aphidicolin. (
  • Prolonged (over 24 h) treatment with aphidicolin increased NO production and endothelial NO synthase (eNOS) protein expression, which was accompanied by increased eNOS dimer/monomer ratio, tetrahydrobiopterin levels, and eNOS mRNA expression. (
  • A promoter assay using 5'-serially deleted eNOS promoters revealed that Tax-responsive element site, located at −962 to −873 of the eNOS promoter, was responsible for aphidicolin-stimulated eNOS gene expression. (
  • Co-treatment with LY294002 decreased the aphidicolin-stimulated increase in p-CREB-Ser 133 level, eNOS expression, and NO production. (
  • Furthermore, ectopic expression of dominant-negative Akt construct attenuated aphidicolin-stimulated NO production. (
  • Lastly, aphidicolin increased acetylcholine-induced vessel relaxation in rat aortas, which was accompanied by increased p-ATM-Ser 1981 , p-Akt-Ser 473 , p-CREB-Ser 133 , and eNOS expression. (
  • At concentrations that did not greatly affect mitotic index, aphidicolin induced a striking number of chromosome gaps and breaks distributed in a highly nonrandom manner in cultured human lymphocytes. (
  • 7. Precise localization of aphidicolin-induced breakpoints on the short arm of human chromosome 3. (
  • The sites most sensitive to aphidicolin damage include the 'hot spots' seen under conditions of thymidylate stress and in studies of spontaneous chromosomal damage. (