Replicative dna polymerase inhibitor. Medical search. Frequent questions

Many cancer types exhibit high levels of replicative stress, and inducing replicative stress can induce cancer cell death, especially when DNA damage responses are impaired. (recombinationtx.com)

Fluorescence-activated cell sorting (FACS) is a technique for sorting out the cells based on the differences that can be detected by light scatter (e.g. cell size) or fluorescence emission (by penetrated DNA, RNA, proteins or antigens). (wikipedia.org)
Polq is a multi-functional DNA repair factor that is essential for the survival of homologous recombination (HR) deficient cancer cells, such as those mutated in the BRCA1/2 tumor suppressor proteins. (recombinationtx.com)
BRCA1 and BRCA2 proteins are involved in restoration of DNA damage through the HR pathways and cells defective in these two proteins are unable to solve replication forks stalling caused by agents that produce interstrand crosslinks. (estme.org)
If PARP activity is definitely lost by using specific inhibitors, the formation of DNA lesions raises and, when this event is definitely contemporary with deficiency of BRCA1 or BRCA2 proteins, a synthetic lethality situation happens for the malignancy cells [7]. (estme.org)
Chromosome replication is triggered when a nucleoprotein complex, termed the orisome, assembles, unwinds the duplex DNA, and recruits the proteins required to establish new replication forks. (mdpi.com)
DDX5 is required for cell proliferation by controlling the transcription of genes expressing DNA replication proteins in cancer cells in which the DDX5 locus is amplified, and this has uncovered a dependence on DDX5 for cell proliferation. (aacrjournals.org)
The presence of replication stress activates the DNA damage response and downstream checkpoint proteins including ataxia telangiectasia and Rad3 related kinase (ATR), checkpoint kinase 1 (CHK1), and WEE1-like protein kinase (WEE1), which trigger cell cycle arrest while protecting and restoring stalled replication forks. (bmj.com)
Any obstacles encountered by cells in this process can lead to 'replicative stress' ( Figure 1 ), 1 which may be overcome by replicative stress response proteins, but deficiencies in this response result in accumulated errors in DNA replication and loss of genomic integrity, which lead to cell death. (bmj.com)
The purpose of this particular simple interaction is to produce an update for the improvement involving INHAND.Inch"Human exonuclease One (hEXO1) is suggested as a factor within DNA fat burning capacity, including duplication, recombination and repair, substantiated by simply their relationships along with PCNA, Genetics helicases BLM as well as WRN, and lots of Genetic make-up mismatch fix (MMR) proteins. (pdgfrsignals.com)
Recruitment regarding hEXO1 in order to DNA DSB web sites depends on the actual MMR proteins hMLH1. (pdgfrsignals.com)
We show 2 specific hMLH1 interaction parts of hEXO1 (elements 390-490 as well as 787-846) are required to direct the particular proteins towards the DNA injury web site. (pdgfrsignals.com)
Although the senescent cells remain viable, they show typical changes with enlarged and flattened cell bodies, apoptosis resistance, increased activity of senescence-associated β -galactosidase (SA- β -gal), and upregulation of cyclin-dependent kinase (CDK) inhibitors including p16 INK4A , ARF proteins, and p21 [ 13 - 16 ]. (hindawi.com)
The nucleotide sequences of DNA guide the synthesis of cellular RNAs and proteins, making DNA a marvelous control device necessary to maintain a number of vital functions of living cells. (techscience.cn)
Proteins which bind to DNA. (lookformedical.com)
The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. (lookformedical.com)
There was, however, a clear transcriptional response, including repression of DNA replication and chromatin proteins. (biomedcentral.com)
A clear response to DNA damage was observed, with down-regulation of the DNA replication machinery, changes in transcriptional regulatory proteins, and up-regulation of the biosynthetic enzymes for beta-carotene, which has UV protective properties, and proteins that detoxify reactive oxygen species. (biomedcentral.com)
However, unlike eukaryotes and bacteria, there was no induction of DNA repair proteins in response to DNA damage, probably because these are expressed constitutively to deal with increased damage arising due to high growth temperatures. (biomedcentral.com)
In addition to DNA repair proteins, bacteria and eukaryotes have damage response pathways whose function is to detect DNA damage and modulate cellular processes. (biomedcentral.com)
In general, the aim is to ensure that DNA repair proteins are activated and that DNA replication is delayed until repair can be completed. (biomedcentral.com)
When DNA damage occurs, a damage signal corresponding to the strand exchange protein RecA bound to single-stranded DNA causes the LexA repressor to be degraded, resulting in the induction of transcription of a large number of repair proteins. (biomedcentral.com)
There are no clear archaeal homologues of either bacterial LexA or of eukaryal proteins involved in the transcriptional response to DNA damage, such as p53. (biomedcentral.com)
In contrast, TC-NER is initiated by blockage of elongating RNA polymerase II at photoadducted sites, followed by recruitment of the CSB (Rad26) and CSA (Rad28) proteins. (colinsbraincancer.com)
ATR/Mec1 phosphorylates a variety of proteins substrates after that, a lot of which promote DNA replication conclusion and therefore cell success (11, 12). (colinsbraincancer.com)

Polq also promotes cellular resistance to various cancer therapies, such as ionizing radiation, topoisomerase inhibitors and PARP inhibitors. (recombinationtx.com)
successfully applied to the inhibition of poly(ADP-ribose) polymerase (PARP-1), which is definitely involved in the identification of damages deriving from reactive oxygen species [14]. (estme.org)
Recently, some small molecules based on nicotinamide analogs have been reported to function as inhibitors of PARP-1 [15,16]. (estme.org)
An interesting result was acquired using PARP-1 inhibitors against BRCA1 and BRCA2 deficient tumor cells, in which killing was specifically directed again these cells with minimal effects on wild-type cells [17,18]. (estme.org)
The alternative pathway necessary to repair DSBs is definitely NHEJ or a single-strand annealing (SSA) process that requires the intervention of the poly (ADP-ribose) polymerase PARP. (estme.org)
The purpose of this study was to explore the efficacy and tolerability of poly ADP-ribose polymerase (PARP) inhibitors in patients with ovarian cancer. (biomedcentral.com)
Moreover, the analysis found that the use of PARP inhibitors did not significantly increase the risk of all grade adverse events (AEs) (RR = 1.04, p = 0.16). (biomedcentral.com)
PARP inhibitors can improve the prognosis of ovarian cancer patients with and without genetic mutations (BRCA 1/2 or HRD). (biomedcentral.com)
Furthermore, PARP inhibitors were tolerable to patients when added to their current therapy, although it inevitably adds the grade 3 and higher AEs. (biomedcentral.com)
On the other hand, studies have shown that PARP (poly ADP-ribose polymerase) was a key regulator of DNA damage repair, and PARP enzymes played a vital role in repairing single-strand breaks through base excision repair [ 9 ]. (biomedcentral.com)
PARP inhibitors captured PARP on the DNA of the single-strand break site, thereby preventing the repair of these breaks and producing double-strand breaks, which were not accurate in tumors with homologous recombination deficiency (HRD) repair [ 11 ]. (biomedcentral.com)
To understand the determinants of response to topoisomerase inhibitors, he is studying the repair pathway centered on tyrosyl-DNA-phosphodiesterases (TDP1 and TDP2) and poly(ADP-ribose)polymerases (PARP). (cancer.gov)

This study used etoposide, to induce DNA damage-related senescence or chronic exposure to IL-1β to entail inflammation-related senescence in human OA chondrocytes. (aging-us.com)
Several hallmarks of cellular senescence, such as cell cycle arrest, expression of cyclin-dependent kinase inhibitors, DNA damages, and senescence-associated secretory profile were evaluated. (aging-us.com)
On the other hand, etoposide treatment reliably induces DNA damage-related senescence in human articular chondrocytes evidenced by loss of proliferative capacity, DNA damage accumulation, and expression of some SASP components. (aging-us.com)
SnCs exhibit irreversible growth arrest accompanied by increased expression of cyclin-dependent kinase inhibitors (CDKi) such as p16 INK4a , and p21 Cip1 , accumulation of DNA damages, and secretion of diverse bioactive molecules known as the senescence-associated secretory phenotype (SASP). (aging-us.com)
One of them is the replicative aging of cells (senescence), which consists in the irreversible stopping of cell division at the G1 stage of the cell cycle. (vechnayamolodost.ru)
In this issue, we generally review the mechanisms of cellular senescence in diabetic nephropathy, which involve telomere attrition, DNA damage, epigenetic alterations, mitochondrial dysfunction, loss of Klotho, Wnt/ β -catenin signaling activation, persistent inflammation, and accumulation of uremic toxins. (hindawi.com)
We demonstrate that PLL provides favourable microenvironment for MSC culture by reversing the replicative senescence. (hindawi.com)
Unlike embryonic stem cells, adult stem cells (MSCs) have a limited lifespan and stop proliferating during in vitro culture due to replicative senescence [ 8 ]. (hindawi.com)
Moreover, replicative senescence of MSCs exhibits reduced functionality, and cellular senescence might impair the regenerative potential of MSCs [ 10 ]. (hindawi.com)
Studies show that replicative senescence or cellular senescence is induced by intrinsic or extrinsic environmental factors [ 11 ]. (hindawi.com)
Cell senescence can be a result of the exposure to stress such as oxidative stress, epigenomic damage or DNA damage, or it can be due to telomere shortening is also known as end replication problem. (ijpsr.com)
1 In their studies, they observed that human diploid cells replicate a finite number of times before they undergo irreversible arrest, 1 it was termed as Hayflick limit also known as replicative senescence (RS) 2 . (ijpsr.com)
Due to DNA damage response, senescence-like phenotype has been seen in cortical neurons. (ijpsr.com)

We recently reported that genetic or pharmacological inhibition of insulin-like growth factor receptor (IGF-1R) slows DNA replication and induces replication stress by downregulating the regulatory subunit RRM2 of ribonucleotide reductase, perturbing deoxynucleotide triphosphate (dNTP) supply. (nature.com)
He revealed the interfacial inhibition paradigm based on molecular mechanisms of topoisomerase inhibitors, and has championed its broad relevance for molecular pharmacology and drug discovery. (cancer.gov)
Inhibition of eukaryotic DNA polymerase-alpha by polydeoxynucleotides. (neb.com)
RNA polymerase inhibition plays an important role in the regulation of transcription in response to environmental changes and in the virus-host relationship. (diamond.ac.uk)
Here we present the high-resolution structures of two such RNAP-inhibitor complexes that provide the structural bases underlying RNAP inhibition in archaea. (diamond.ac.uk)
Veuger et al (2003) Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA-dependent protein kinase and poly(ADP-ribose) polymerase-I. Cancer Res. (tocris.com)

Elevated levels of replicative stress in gynecological cancers arising from uncontrolled oncogenic activation, loss of key tumor suppressors, and frequent defects in the DNA repair machinery are an intrinsic vulnerability for therapeutic exploitation. (bmj.com)

Replication is catalysed by processive replication enzymes known as DNA polymerases and is limited to the synthesis phase (S phase) of the cell cycle. (lancs.ac.uk)
There is also a pathway called translesion synthesis (TLS), that is an ubiquitous mechanism that support DNA synthesis past lesions that cannot be negotiated from the high-fidelity replicative DNA pols. (estme.org)
Preferential loss of DNA polymerase alpha following suppression of replicative DNA synthesis of guinea pig macrophages by the immunostimulants muramyl dipeptide or lipopolysaccharide. (neb.com)
Specific inhibitors of eukaryotic DNA synthesis and DNA polymerase alpha, 3-deoxyaphidicolin and aphidicolin-17-monoacetate. (neb.com)
Indeed, a number of agents currently used in cancer treatment are known to target DNA synthesis. (aacrjournals.org)
Synthesis of each Okazaki fragment starts with the low fidelity Pol α synthesizing a ~30 nt RNA/DNA initiator primer. (nature.com)
However, how eukaryotic Pol δ achieves processive DNA synthesis and how it cooperates with PCNA and other factors during Okazaki fragment processing remains unknown. (nature.com)
POLQ also mediates translesion DNA synthesis and it is largely not expressed in normal cells. (techscience.cn)
Moloney Murine Leukemia Virus Reverse Transcriptase (MMLV RT) is an RNA-dependent DNA polymerase that can be used for cDNA synthesis and subsequent PCR or qPCR in one-step or two-step RT-PCR or RT-qPCR assays. (meridianbioscience.com)
Eukaryotic cells have thus developed the extremely conserved DNA harm response (DDR), a significant branch which (the S stage checkpoint) works to decelerate DNA synthesis, thus providing more possibility to mitigate the genotoxic implications of replicative tension. (colinsbraincancer.com)

We show that our assay is applicable to different eukaryotic and bacterial exonucleases acting on both 3′ and 5′ DNA ends over a wide range of protein activities and suitable for a high-throughput inhibitor screening campaign. (edu.sa)
2022. Ribonucleotide incorporation by eukaryotic B-family DNA replicases and its consequences. (nih.gov)
The mode of inhibitory action by aphidicolin on eukaryotic DNA polymerase alpha. (neb.com)
Maintaining genomic integrity is of utmost importance to eukaryotic cells, which have evolved sophisticated mechanisms to ensure speed, accuracy, and an adequate pool of nucleotide and replication factors as well as high-fidelity repair pathways to correct errors occurring during DNA replication. (bmj.com)
Unlike eukaryotic replicative polymerases, reverse transcriptase lack exonuclease activity and so is error prone. (meridianbioscience.com)
An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES. (lookformedical.com)

discovered mechanism of Polq-mediated DNA end-joining. (recombinationtx.com)
DNA polymerase-theta (POLQ) is an error-prone DNA polymerase involved in double-strand break repair through microhomology-mediated end joining (MMEJ). (techscience.cn)
In HR deficient cells, MMEJ is crucial as a backup DNA repair pathway, indicating the indispensable role of POLQ-mediated MMEJ in HR deficient cancer cells. (techscience.cn)
This multi-functional DNA polymerase plays a key role in tumors with deficient homologous recombination (HR). This viewpoint aims to rationalize POLQ as a druggable target for HR-deficient tumors by providing recent research advancements related to POLQ. (techscience.cn)

Mechanism of microhomology-mediated end-joining promoted by human DNA polymerase θ. (recombinationtx.com)

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. (lancs.ac.uk)
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. (aquagadget.com)
Aphidicolin prevents mitotic cell division by interfering with the activity of DNA polymerase-alpha. (neb.com)

Here using an in vitro cell-free DNA replication system we analyse the interplay between Ciz1 and cyclin A/CDK2 in regulation of the initiation phase of DNA replication. (lancs.ac.uk)
DNA pol can replacement for DNA pol vitro BER using a 25% performance [34]. (estme.org)
TFB3, which is strongly induced following UV irradiation, competes with TFB1 for binding to RNA polymerase in vitro , and may act as a repressor of transcription or an alternative transcription factor for certain promoters. (biomedcentral.com)

Restoration pathways are classically divided into nucleotide excision restoration (NER), mismatch restoration (MMR), foundation excision restoration (BER) and DNA double strand break restoration (DSBR) that includes homologous recombination (HR) and non-homologous end becoming a member of (NHEJ). (estme.org)
R1487 Hydrochloride These pathways have different substrate specificities and modes of action, however all of them require factors able to replace the lost or damaged DNA sequence with original or right copies, usually derived from the unaltered complementary DNA strand. (estme.org)
In each DNA restoration pathways one or more specific DNA pols are required depending on damage kind, cellular cycle phase, DNA restoration reaction and cells specificity. (estme.org)
The multiple DNA restoration pathways in the cell are specialized in repairing specific DNA lesions ITGAE by using different DNA pols as summarized in Table 1. (estme.org)
Table 1 Specialized DNA pols and their involvement in specific DNA restoration pathways. (estme.org)
In parallel, Dr. Pommier has profoundly contributed to the elucidation of the repair pathways for topoisomerase-=induced DNA damage (Pommier et al. (cancer.gov)
2018). While studying the tyrosyl-DNA-phosphodiesterase (TDP1 and TDP2) repair pathways for the excision of topoisomerases from DNA, Dr. Pommier revealed that TDP1 repairs a broad range of 3'-blocking lesions in addition to TOP1 (Murai et al. (cancer.gov)
Irregularities in the DNA repair pathways are frequently observed in cancer. (techscience.cn)
Dysregulated DNA repair pathways support growth advantages to tumor cells. (techscience.cn)
Whilst archaea have eukaryal-type informational pathways such as DNA replication and transcription, archaeal DNA repair pathways are still poorly understood. (biomedcentral.com)

Moreover, the identification of fork protection as a key mechanism of resistance to chemo- and poly (ADP-ribose) polymerase inhibitor therapy in ovarian cancer further increases the priority that should be accorded to the development of strategies targeting replicative stress. (bmj.com)

Dr. Pommier conceptualized the "interfacial inhibitors" mechanism based on his finding that DNA topoisomerase inhibitors act by trapping topoisomerase-DNA complexes (Capranico et al. (cancer.gov)
Current models suggest that blockage of fork development by DNA adducts uncouples the experience of replicative helicase complexes from that of DNA polymerases, which creates parts of single-stranded DNA (ssDNA) (8, 9). (colinsbraincancer.com)

Dr. Pommier is a leader on DNA topoisomerase biology and biochemistry, and their cancer relevance. (cancer.gov)

The cellular enzymes involved in DNA replication generate thousands of copies of DNA with greater fidelity. (techscience.cn)
DNA damage leads to cellular responses that include the increased expression of DNA repair genes, repression of DNA replication and alterations in cellular metabolism. (biomedcentral.com)
It is noteworthy that several essential NER factors (RPA1C3, proliferating cell nuclear antigen, and DNA ligase) also play independent functions in other crucial cellular processes, such as DNA replication and homologous recombination. (colinsbraincancer.com)

It is worth remembering, among other things, that mutation mutations are different, and according to the latest genomic research, in each generation a person acquires about 60 new mutations (which were not in the DNA of his parents). (vechnayamolodost.ru)
None detected in PCR amplification with traces overlay with the negative control on E. coli and mouse genomic DNA specific targets. (meridianbioscience.com)
The maintenance of genomic integrity is a crucial task for every living thing, and all organisms devote considerable resources to the repair of DNA damage. (biomedcentral.com)
Two unique NER subpathways have been recognized: global genomic NER (GG-NER) and transcription-coupled NER (TC-NER), which excise UV DNA photoproducts throughout the entire genome and exclusively from your ENOblock (AP-III-a4) transcribed strands of active genes, respectively. (colinsbraincancer.com)

These data suggest that Ap4A inhibits initiation by reducing loading of the replicative helicase MCM2-7 and the DNA polymerase sliding clamp PCNA. (lancs.ac.uk)
Polymerase θ-helicase efficiently unwinds DNA and RNA-DNA hybrids. (recombinationtx.com)
Promising new inhibitors that target the viral helicase-primase complex have been reported to block replication of herpes simplex and varicella-zoster viruses, but they have no activity against human cytomegalovirus (HCMV), another herpesvirus. (frontiersin.org)
The HCMV helicase-primase complex (pUL105-pUL102-pUL70) is essential for viral DNA replication and could thus be a relevant antiviral target. (frontiersin.org)

Furthermore, direct proof is so long as this cell cycle-specific fix defect is prompted by sequestration of RPA1C3 to regions of ssDNA during periods of enhanced replicative stress, ostensibly causing reduced availability of this complex to perform its essential ENOblock (AP-III-a4) function in NER. (colinsbraincancer.com)

These effects resulted in significant accumulation of unreplicated single-stranded DNA and increased cell death, indicative of replication catastrophe. (nature.com)

For example, in the hereditary cancer syndromes familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, mutations have been discovered in the APC gene and DNA mismatch repair genes. (medscape.com)
We also reported that inactivating mutations in or of any among other DDR genes mixed up in mobile response to replicative tension cripples NER exclusively in S stage. (colinsbraincancer.com)

Phosphorylation stabilizes DNA pol during both the S and G2 phases of the cell cycle, permitting the enzyme to act in numerous biochemical processes, such as NHEJ, BER and TLS [33,34,35]. (estme.org)
This enzyme showed an efficient capability to elongate the DNA from a RNA primer annealed towards the double-stranded DNA [37,38]. (estme.org)
Studying an enzyme's kinetics in this way can reveal the catalytic mechanism of this enzyme, its role in metabolism , how its activity is controlled, and how a drug or a modifier ( inhibitor or activator ) might affect the rate. (wikipedia.org)
DNA polymerase-beta from the nuclear fraction of sea urchin embryos: characterization of the purified enzyme. (neb.com)
The gene coding for the DNA repair enzyme that recognizes and excises 8-oxo-dG is 8-oxoG-DNA glycosylase (OGG1) [ 14 ]. (biomedcentral.com)
CQ068 is subunits of an alpha accessory factor (AAF) that stimulates the activity of DNA polymerase-alpha-primase (see MIM 176636), the enzyme that initiates DNA replication. (thermofisher.com)

Here, we present a simple and versatile real-time exonuclease assay based on 2-aminopurine, an intrinsically fluorescent nucleotide that is quenched by neighboring bases when embedded in DNA. (edu.sa)
Others join two substrates together, such as DNA polymerase linking a nucleotide to DNA . (wikipedia.org)
Dr. Pommier also discovered that the natural compound, ecteinascidin 743 (commercialized as Yondelis) and its analog trabectedin acts by alkylating DNA and killing cancer cells by trapping transcription-coupled nucleotide excision repair (TC-NER) (Takebayashi et al, Nature Med 2001). (cancer.gov)
The crenarchaeal Sulfolobus species probably suffer more than most, due to growth at 80°C, leading to more rapid reactions such as hydrolytic deamination of nucleotide bases, an aerobic lifestyle resulting in DNA damage by reactive oxygen species (ROS) and exposure to UV irradiation. (biomedcentral.com)

Using semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) and western blots experiments, we compared changes in ETS-1 and ETS-2 expression, their protein levels, and the regulation of some of their target gene expressions at different stages of the ocular tumoral progression in the transgenic mouse model, Tyrp-1-TAg, with those in normal eyes from control mice of the same age. (molvis.org)

This demonstrates that Ciz1 modulates and enhances the activity of cyclin A-CDK2 in cell free DNA replication assays and that Ciz1 increases the permissive CDK range that can promote DNA replication. (lancs.ac.uk)
In the p53 pathway, the gene activates its transcriptional target p21 which is an inhibitor of cyclin / cdk2 as they work for the progression of replication and inactivates RB. (ijpsr.com)

He was the first to show that topoisomerases are trapped by DNA damage (by oxidative base lesions, base alkylation, DNA nicks) (Pourquier et al. (cancer.gov)
During cell division, tissue rejuvenation occurs: new cells take the place of damaged ones, while repair (elimination of DNA damage) occurs more intensively and regeneration is possible in case of tissue damage. (vechnayamolodost.ru)
Strategies that increase replicative stress while lowering cell cycle checkpoint thresholds may allow unrepaired DNA damage to be inappropriately carried forward in replicating cells, leading to mitotic catastrophe and cell death. (bmj.com)
Small molecule inhibitors designed to target the DNA damage sensors, such as inhibitors of ataxia telangiectasia-mutated (ATM), ATR, CHK1 and WEE1, impair smooth cell cycle modulation and disrupt efficient DNA repair, or a combination of the above, have demonstrated interesting monotherapy and combinatorial activity, including the potential to reverse drug resistance and have entered developmental pipelines. (bmj.com)
In the presence of errors or damage during DNA replication, cell cycle checkpoint nodes and repair machinery work in concert to retard cell cycle progression until sufficient repair has been achieved. (bmj.com)
The shortening of telomeres constitutes an intrinsic factor, whereas DNA damage is considered an extrinsic factor. (hindawi.com)
Sulfolobus species encounter high levels of DNA damage in nature, as they inhabit high temperature, aerobic environments and are exposed to sunlight. (biomedcentral.com)
Differential effects on the expression of the three transcription factor B ( tfb ) genes hint at a mechanism for the modulation of transcriptional patterns in response to DNA damage. (biomedcentral.com)
Many environmental factors contribute to the overall load of DNA damage suffered by a cell. (biomedcentral.com)
Despite this high damage load, the rate of mutation in Sulfolobus acidocaldarius is no higher than for mesophilic organisms such as Escherichia coli [ 1 ], indicating that DNA damage is repaired efficiently. (biomedcentral.com)
Under normal growth conditions, where levels of DNA damage are low, transcription of repair genes is repressed. (biomedcentral.com)
Experimental studies of the archaeal DNA damage response have been very limited. (biomedcentral.com)

He demonstrated the interfacial inhibitor mechanism by co-crystal studies (Ionaviciu et al. (cancer.gov)
The integrity of the genetic information stored in DNA depends on the DNA repair mechanism. (techscience.cn)

We identify an important role for DDX5 in G 1 -S-phase progression where it directly regulates DNA replication factor expression by promoting the recruitment of RNA polymerase II to E2F-regulated gene promoters. (aacrjournals.org)
Helix-distorting CPDs and 6-4PPs strongly block the progression of DNA polymerases, which causes prolonged replication fork stalling and formation of DNA strand breaks, eventually leading to cell death (7). (colinsbraincancer.com)

We applied an assay that measures the stability of maintenance of an episomal plasmid in human tissue culture cells to screen for new DNA replication factors. (aacrjournals.org)

You can add RNase Inhibitor (MDX056), alternatively we also have RNase-Tolerant MMLV-RT (MDX043) which includes an RNase inhibitor. (meridianbioscience.com)

For example, in the figure showing trypanothione reductase from the human protozoan parasite Trypanosoma cruzi, two molecules of an inhibitor called quinacrine mustard are bound in its active site. (pdgfrsignals.com)
Unlike RNA and protein, damaged DNA molecules are irreplaceable. (techscience.cn)

Polθ promotes the repair of 5'-DNA-protein crosslinks by microhomology-mediated end-joining. (recombinationtx.com)

For this reason, DNA pols are the key players in DNA restoration [19]. (estme.org)
In fact, DNA pols are the only biological macromolecules able to duplicate the genetic information stored in the DNA, hence they are necessary during both DNA replication and restoration. (estme.org)

2. DNA Polymerases as Anticancer Drug Targets You will find multiple mechanisms for fixing the unique DNA lesions deriving from different sources. (estme.org)
2022. Probing the mechanisms of two exonuclease domain mutators of DNA polymerase ε. (nih.gov)
This review provides an overview of the basic molecular mechanisms involved in mitochondrial fusion and focuses on the alteration in mitochondrial DNA amount resulting from impairment of mitochondrial dynamics. (centrodinoferrari.com)
In healthy cells, robust and diverse DNA repair mechanisms faithfully protect from DNA damages to maintain overall survival. (techscience.cn)
The availability of diverse DNA repair systems reflects the complex nature of DNA repair mechanisms in healthy cells. (techscience.cn)

For quantitative cell cycle analysis, cells are usually fixed with ethanol and stained with DNA-binding dyes like propidium iodide, Hoechst 33342, DAPI, 7-Aminoactinomysin D, Mithramycin, DRAQ5, or TO-PRO-3, allowing for determination of phase by DNA quantity. (wikipedia.org)
First, given evidence that IGFs regulate the response to IR, we also found evidence that IGF-1R depletion induced endogenous DNA lesions marked by γH2AX foci in prostate cancer cells [ 10 ]. (nature.com)
During the mitotic mammalian cell cycle cells faithfully replicate their DNA utilizing multiple DNA replication sites known as origins of replication. (lancs.ac.uk)
Understanding how DNA replication is regulated in human cells can provide insight into cancer development and may reveal vulnerabilities that can be exploited therapeutically. (aacrjournals.org)
They further link to the activation of protein kinase C- (PKC-) induced generation of reactive oxygen species (ROS) [ 6 , 7 ], which further mediates the activation of downstream transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF- κ B). Thus, the main treatments of DN refer to modulate glycemic and blood pressure through insulin and RAS inhibitors. (hindawi.com)
DNA stores genetic information in cells. (techscience.cn)
Mammalian cells contain 15 different DNA polymerases. (techscience.cn)

Exonucleases are essential enzymes that remove nucleotides from free DNA ends during DNA replication, DNA repair, and telomere maintenance. (edu.sa)
During DNA REPLICATION, chromosome ends loose some of their telomere sequence (TELOMERE SHORTENING. (lookformedical.com)

NU 7026 is an ATP-competitive inhibitor of DNA-dependent protein kinase (DNA-PK). (tocris.com)
These data indicate that tuberin deficiency in angiomyolipoma enhances mTOR activation by phosphorylation of S6K and downregulation of protein and mRNA expression of OGG1 resulted in accumulation of oxidized DNA in patients with TSC. (biomedcentral.com)
Quantify DNA, RNA, and protein in seconds using only 1-2 µL of sample-no need for dilution. (thermofisher.cn)
INTRODUCTION: The major complication of protein replacement therapy for haemophilia A is the development of anti-FVIII antibodies or inhibitors that occur in 25%-30% of persons with severe haemophilia A. Alternative therapeutics such as bypassing agents or immune tolerance induction protocols have additional challenges and are not always effective. (cdc.gov)

Changes in the timing of replication, origin usage and replication rate are indicative of DNA replication stress, a proposed hallmark of cancer that causes genome instability. (lancs.ac.uk)

These include control of the transcriptional repertoire of the cell, activation of repair enzymes and repression of DNA replication and cell division. (biomedcentral.com)

In eukaryotes, DNA polymerase δ (Pol δ) bound to the proliferating cell nuclear antigen (PCNA) replicates the lagging strand and cooperates with flap endonuclease 1 (FEN1) to process the Okazaki fragments for their ligation. (nature.com)
We present the high-resolution cryo-EM structure of the human processive Pol δ-DNA-PCNA complex in the absence and presence of FEN1. (nature.com)
This arrangement allows PCNA to thread and stabilize the DNA exiting the catalytic cleft and recruit FEN1 to one unoccupied monomer in a toolbelt fashion. (nature.com)
In the maturation of Okazaki fragments, Pol δ invades the previously synthesized Okazaki fragments to gradually displace the RNA-DNA primers for their removal by the PCNA-bound FEN1 16 . (nature.com)
Fig. 1: Cryo-EM structure of the processive Pol δ-DNA-PCNA complex. (nature.com)

As Chief, Dr. Pommier oversees the Branch's clinical/translational research program, which emphasizes new approaches to cancer treatments targeting DNA, epigenetic and chromatin, and connected biomarkers. (cancer.gov)
With the loss of replicative inability changes in metabolism, gene expression and epigenetic regulation also take place. (ijpsr.com)

Errors in DNA can cause undesirable effects as they can affect the function of a gene. (techscience.cn)
RESULTS: Working Group 1 was charged with determining the scientific priorities for clinical trials to include the integration of non-intravenous, non-factor therapeutics including gene therapy into the standard of care for people with haemophilia A with inhibitors. (cdc.gov)

DNA is replicated to provide each daughter cell a complete copy of the genome. (lancs.ac.uk)
Replication of DNA is initiated at multiple sites along the genome, known as replication origins, which form bidirectional replication forks. (bmj.com)
Tissue Specific DNA Repair Outcomes Shape the Landscape of Genome Editing. (cemm.at)

Differential susceptibilities of DNA polymerases-alpha and -beta to polyanions. (neb.com)

8-Oxo-dG in DNA is repaired primarily via the DNA base excision repair pathway. (biomedcentral.com)

One technique that is garnering wide attention in this realm is the DNA array, in which a number of different genes from an individual can be processed to look at certain genotypes. (medscape.com)
No increase in expression of DNA repair genes following UV irradiation was observed. (biomedcentral.com)

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Chemicals and Drugs72

Analytical, Diagnostic and Therapeutic Techniques and Equipment5

Phenomena and Processes34

Information Science3

Health Care1

Inducing replicative stress1

Proteins24

PARP12

Senescence13

Inhibition6

Levels of replicative stress1

Synthesis10

Eukaryotic6

Polq4

Human DNA polymerase1

Aphidicolin3

Vitro3

Pathways10

Poly1

Complexes2

Topoisomerase1

Cellular3

Genomic4

Helicase4

SsDNA1

Single-stranded1

Mutations2

Enzyme6

Nucleotide4

Reverse transcri1

Cyclin2

Damage12

Mechanism2

Progression2

Assay1

RNase1

Molecules2

Microhomology-mediated1

Pols2

Mechanisms5

Cells7

Telomere2

Protein4

Proposed hallma1

Replication and Cell Division1

PCNA5

Epigenetic2

Gene2

Genome3

Differential1

Repair pathway1

Genes2