• Cell cycle progression, phosphorylation, and DNA binding of cell cycle checkpoint proteins were analyzed. (nih.gov)
  • Proteins involved in the ATM-and-Rad3-related kinase (ATR)-dependent S-phase checkpoint response (Chk1 and Rad17) were also phosphorylated but not ataxia telengectasia mutated kinase. (nih.gov)
  • Our laboratory is interested in understanding the mechanisms by which microRNA and checkpoint proteins stall the cell cycle preventing genomic instability and cancer. (nii.res.in)
  • Whenever genomic lesions are detected during DNA synthesis, they are coated by the single strand DNA binding protein complex, called Replication Protein A, leading to the activation of canonical checkpoint proteins like ATR, Chk1 and p53. (nii.res.in)
  • Human genome codes for many other single strand DNA binding proteins and we are testing if novel mechanisms of checkpoint activation exist that do not require Replication Protein A. If such mechanisms exist we would like to understand which factors provide the role of DNA binding, how checkpoint proteins like Chk1 and p53 are activated and how signal transduction pathway stalls the cell cycle and DNA replication. (nii.res.in)
  • It has been observed that some replication proteins localize to the centrosome suggesting their role in regulation of centrosome biogenesis. (nii.res.in)
  • I'm using cell and molecular biology techniques, biochemistry as well as microscopy to characterise the plant SUN proteins. (brookes.ac.uk)
  • This includes finding out what other proteins the SUNs bind to and what functions they have during cell division. (brookes.ac.uk)
  • The duplication of chromosomes and the regulation of their replication and repair requires dozens of proteins acting together to maintain the duplex DNA genome. (rockefeller.edu)
  • Proliferating cell nuclear antigen (PCNA) is a member of the DNA sliding clamp family of proteins that assist in DNA replication (6). (cellsignal.com)
  • Multiple proteins involved in DNA replication, DNA repair, and cell cycle control bind to PCNA rather than directly associating with DNA, thus facilitating fast processing of DNA (reviewed in 7). (cellsignal.com)
  • The authors identified proteins associated with the yeast origin recognition complex (ORC), a set of proteins that binds chromosomal origins of DNA replication. (rupress.org)
  • Among the proteins identified was Yph1p, a homologue of zebrafish pescadillo, mutations in which lead to cell proliferation defects. (rupress.org)
  • Yph1p was also found in complex with a variety of other proteins, including those involved in ribosome biogenesis, cell cycle regulation, and checkpoint control. (rupress.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)
  • Each origin is initiated by a combination of regulatory proteins that prepare the chromatin for replication before synthesis (S)-phase entry. (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)
  • Trainees in my laboratory will gain knowledge about chromatin biology, DNA repair, and cancer-causing gene rearrangements, and will develop expertise in cell culture, molecular biology techniques for proteins and nucleic acids, cytogenetic analysis, and electron microscopy. (virginia.edu)
  • In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. (tocris.com)
  • If the repair is defective and the cell accumulates many genomic errors, "watch-out" proteins step in, such as tumor suppressor p53. (rdworldonline.com)
  • Such proteins activate programmed cell death (apoptosis) or cell cycle arrest (senescence). (rdworldonline.com)
  • The precise regulation of the levels of cyclin proteins is fundamental to coordinate cell division with checkpoints, avoiding genome instability. (ox.ac.uk)
  • We are interested in understanding at the molecular level how recombination occurs and what roles are played by the many proteins involved in DNA recombination, repair and replication. (brandeis.edu)
  • We are interested in determining what are the specific biochemical roles played by the many proteins implicated in DNA recombination, repair and replication. (brandeis.edu)
  • We have identified the proteins necessary to carry out the initial steps in strand invasion and the beginning of new DNA synthesis, which is significantly different from the normal process of replication. (brandeis.edu)
  • In this study, we hypothesized that 5-ASA restrains cell cycle progression by activating checkpoint pathways in colorectal cell lines, which would prevent tumor development and improve genomic stability. (nih.gov)
  • Even as the nature of the exact cell in which Merkel cell carcinoma oncogenesis occurs is controversial, there is strong support for the notion that Merkel cell carcinoma results from of one of two distinct pathways. (medscape.com)
  • TP53 inhibition allows LINE-1 + cells to grow, and genome-wide-knockout screens show that these cells require replication-coupled DNA-repair pathways, replication-stress signaling and replication-fork restart factors. (nih.gov)
  • The lab's findings also provide insights into how replisomes achieve the asymmetric inheritance needed for development, and how they participate in DNA damage checkpoint control pathways. (rockefeller.edu)
  • In particular we are interested in regulatory pathways that drive cell division and in surveillance mechanisms, also known as checkpoint pathways, that stop cell cycle progression when cellular components malfunction or become damaged. (unt.edu)
  • 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)
  • In this study, published in the journal Proceedings of the National Academy of Sciences (PNAS), the scientists postulate that the initiation of a tumor and the type and aggressivity of the same depend on a specific combination of defects in several processes that safeguard cell integrity, such as DNA repair pathways and cell cycle check-points. (rdworldonline.com)
  • Whether or not a tumor develops depends on the moment of the cell cycle in which the damage occurs, which repair pathways components are affected, and which others are impaired in terms of apoptosis and cell cycle arrest", explains the North-American Travis H. Stracker, head of the "Genomic Instability and Cancer" group and an expert in DNA repair pathways and its implications on human health. (rdworldonline.com)
  • the chorion gene loci in follicle cells (21 22 In pre-RC development the effective launching of multiple MCM complexes is necessary for the toleration of replication strains and activation of checkpoint pathways (23-25). (exposed-skin-care.net)
  • This skin cancer has been called by several other names, including primary small-cell carcinoma of the skin, APUDoma, primary undifferentiated carcinoma of the skin, and the Toker tumor. (medscape.com)
  • With the advent of improved immunohistochemical profiling, the tumor was reclassified as Merkel cell carcinoma because shared epithelial and neuroendocrine markers, along with ultrastructural features suggestive of neural crest origin, were observed in both the constituent tumor cell and the physiologic Merkel cell of the skin. (medscape.com)
  • We identified a colorectal cancer wherein a fast-growing tumor subclone downregulated LINE-1, prompting us to examine how LINE-1 expression affects cell growth. (nih.gov)
  • 5) increasing the intrinsic radioresistance of normal cells through ketone bodies but decreasing that of tumor cells by targeting glycolysis. (springer.com)
  • Preclinical models predict that blockade of the coinhibitory molecule cytotoxic T lymphocyte-associated antigen 4 (CTLA4) on lymphocytes results in the release of a cell cycle inhibitory checkpoint, allowing lymphocyte proliferation, tumor targeting, and regression. (snmjournals.org)
  • Despite occasional cases of expansion of melanoma-specific T cells ( 14 , 15 ), the bulk of the data suggest that there is no detectable expansion of tumor antigen-specific lymphocytes, in particular when focusing on CD8+ T-cell responses. (snmjournals.org)
  • By definition, mutations that cause CIN in cancer cells produce "sub-lethal" deficiencies in an essential cellular process (chromosome maintenance) and therefore may represent genetic vulnerabilities in tumor cells that could be exploited for therapeutic benefit in the treatment of cancer. (ubc.ca)
  • Our HCC signature covered well-established liver cancer hallmarks, and network analyses revealed coordinated interaction between several MRs. One novel MR, SEC14L2 , exerted an anti-proliferative effect in HCC cells and strongly suppressed tumor growth in a mouse model. (aging-us.com)
  • It was identified that the nuclear division cycle 80, cyclin B2 and topoisomerase 2‑α may serve important roles in adrenocortical tumor development. (cancerindex.org)
  • The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. (affbiotech.com)
  • Basal cell carcinoma (BCC) is a nonmelanocytic skin cancer (ie, an epithelial tumor) that arises from basal cells (ie, small, round cells found in the lower layer of the epidermis). (medscape.com)
  • Initial exponential tumor growth is followed by a plateau phase when cell death nearly equals the rate of formation of daughter cells. (msdmanuals.com)
  • We find that together with loss-of-function mutations in p53 and, to some degree, potentiated by cMyc overexpression, Dusp4 deletion aids in cell cycle checkpoint escape while simultaneously potentiating hallmarks of replicative stress, including multinucleation and Chk1 phosphorylation. (biomedcentral.com)
  • Inhibitor of checkpoint kinase CHK1 was identified as a top screen hit. (nature.com)
  • Co-inhibition of IGF and CHK1 caused synergistic suppression of cell viability, cell survival and tumour growth in 2D cell culture, 3D spheroid cultures and in vivo. (nature.com)
  • Investigating the mechanism of synthetic lethality, we reveal that CHK1 inhibition in IGF-1R depleted or inhibited cells further downregulated RRM2, reduced dNTP supply and profoundly delayed replication fork progression. (nature.com)
  • Exogenous RRM2 expression rescued hallmarks of replication stress induced by co-inhibiting IGF with CHK1 or WEE1, identifying RRM2 as a critical target of the functional IGF:CHK1 and IGF:WEE1 interactions. (nature.com)
  • Chk1 inhibition in cells lacking cyclin F leads to DNA replication catastrophe. (ox.ac.uk)
  • We find that SCF-cyclin F controls E2F1 ubiquitylation and degradation during the G2/M phase of the cell cycle and upon challenging cells with Chk1 inhibitors. (ox.ac.uk)
  • 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)
  • Moreover, in adults, Merkel cells undergo slow turnover and are replaced by cells originating from epidermal stem cells, not through the proliferation of differentiated Merkel cells. (medscape.com)
  • Molecular imaging with the PET probe 18 F-FLT allows mapping and noninvasive imaging of cell proliferation in secondary lymphoid organs after CTLA4 blockade in patients with metastatic melanoma. (snmjournals.org)
  • A clear example of the critical role of CTLA4 on tolerance is the striking phenotype of CTLA4 knock-out mice, which develop rapid T-cell proliferation and autoimmune infiltration of multiple organs shortly after birth ( 6 , 7 ). (snmjournals.org)
  • The SignalStain ® Proliferation/Apoptosis IHC Sampler Kit from Cell Signaling Technology allows the researcher to examine paraffin-embedded tissues or cells with antibodies that will detect cellular apoptosis or proliferation. (cellsignal.com)
  • Though Stillman admits the link between DNA replication and ribosome biosynthesis is speculative, he adds that it makes sense, as proliferation requires the replication of both the genome and the cellular machineries. (rupress.org)
  • MTT colorimetric assays, colony formation assays and 5‑ethynyl‑20‑deoxyuridine incorporation assays were also conducted to evaluate ACC cell proliferation. (cancerindex.org)
  • Many factors are involved in causing and permitting the unregulated proliferation of cells that occurs in cancer. (msdmanuals.com)
  • Overview of Cancer Cancer is an unregulated proliferation of cells. (msdmanuals.com)
  • It has been shown that overexpression of CDC6 does not induce re-replication in cognate cells, probably due to inhibition through CDK that resets the cell cycle clock to G1. (wikipedia.org)
  • A dimerized coiled-coil domain and an adjoining part of geminin interact with two sites on Cdt1 for replication inhibition. (nii.res.in)
  • 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)
  • Thus, Cyclin F restricts E2F1 activity during the cell cycle and upon checkpoint inhibition to prevent DNA replication stress. (ox.ac.uk)
  • We have found that a DNA replication checkpoint dependent on the ATM homolog MEC1 operates in wild-type cells during meiosis and can be invoked in response to inhibition of DNA synthesis. (ox.ac.uk)
  • These studies can be expected to provide new insights into eukaryotic replication, repair, and epigenetic inheritance. (rockefeller.edu)
  • Thus, the regulation of CDC6 is tightly correlated to the activity of Cdk2 and since Cdk2-activity is oscillating once per cell cycle, the accumulation and degradation of CDC6 also oscillates. (wikipedia.org)
  • Nevertheless, it has been suggested that regulation of CDC6 is one of several redundant mechanisms that prevent re-replication of the DNA in eukaryotic cells. (wikipedia.org)
  • Ultraviolet Radiation Stress Triggers the Down-regulation of Essential Replication Factor Mcm10. (nii.res.in)
  • Main focus: Cell cycle regulation in budding yeast. (unt.edu)
  • My lab works on cell cycle regulation in budding yeast. (unt.edu)
  • We have shown that this regulation involves the action of a small Recombination Enhancer (RE) sequence that enables a donor on the left chromosome arm to recombine preferentially in MATa cells. (brandeis.edu)
  • We mapped all estrogen receptor and RNA polymerase II binding sites on a genome-wide scale, identifying the authentic cis binding sites and target genes, in breast cancer cells. (nature.com)
  • Emerging evidences suggest that microRNA target genes that regulate DNA replication and cell cycle progression and we aim to determine how microRNA regulate the DNA replication machinery as cell progresses from one phase to the next. (nii.res.in)
  • DUSP4 alterations lead to hyperactivation of MAPK signaling in many cancers, including breast cancer, which often harbor mutations in cell cycle checkpoint genes, particularly in TP53. (biomedcentral.com)
  • Interestingly, replication stress in Brca2-null cells activates p53 and the expression of its target genes, including senescence-inducing Ink4/Arf. (biomedcentral.com)
  • Our functional studies of selected CIN genes in yeast have elucidated mechanistic insights into various aspects of the chromosome cycle, including sister chromatid cohesion, kinetochores, DNA replication and repair, and cell cycle checkpoints. (ubc.ca)
  • To identify candidate drug targets, we have been testing synthetic lethal interactions, predicted in yeast, using RNAi, gene knockouts, and mutants in both C. elegans and mammalian cell culture, to identify evolutionarily conserved SL gene pairs involving CIN genes somatically mutated in cancer. (ubc.ca)
  • The identified DEGs included 20 downregulated genes and 51 upregulated genes, which were highly associated with the cell cycle, organelle fission, chromosome segregation, cell division and spindle stability. (cancerindex.org)
  • STARD12 co-expressed genes participated in cell cycle and DNA replication, and STARD14 were enriched in ECM-receptor interaction. (medsci.org)
  • protein allows mutations to accumulate in other genes, which may cause cells to grow and divide in an uncontrolled way. (diff.org)
  • 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)
  • It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death. (tocris.com)
  • For a cell to progress through the cycle and replicate, it must pass through checkpoints between phases to ensure that DNA is replicated correctly and that chromosomes segregate. (tocris.com)
  • in DNA strands also occur naturally when chromosomes exchange genetic material during cell division. (diff.org)
  • It is known that replication factors are downregulated during stress and we have observed that cullin 4-based ubiquitin ligase mediate the proteolysis of Mcm10, a protein essential for the initiation and elongation phases of DNA replication. (nii.res.in)
  • His lab studies how the replisome interacts with DNA repair and cell cycle checkpoint machinery, how initiation of replication is directed by nucleosomes, and how replication forks perform nucleosome inheritance, the process by which nucleosomes (the fundamental structural unit of chromosomal DNA) are passed down from parental to daughter DNA during replication. (rockefeller.edu)
  • Initiation of DNA replication during the mitotic cell cycle requires the activation of a cyclin-dependent protein kinase (CDK). (ox.ac.uk)
  • Starting from this simple idea, Joshi discovered he could predict the sequence of DNA replication initiation, the end of DNA replication, and division based on when the three timers independently go off and reset. (scitechdaily.com)
  • Moreover several prior reviews implicate SNF2H in stimulating the initiation of DNA replication. (exposed-skin-care.net)
  • For instance CHRAC enables binding of T-antigen and efficient initiation within GSK 525762A an replication program that uses SV40 DNA reconstituted into chromatin (36). (exposed-skin-care.net)
  • Our previous results indicate that 5-ASA improves replication fidelity in colorectal cells, an effect that is active in reducing mutations. (nih.gov)
  • This study identifies a novel mechanism for breast tumorigenesis implicating Dusp4 loss and p53 mutations in cellular acquisition of Dbf4 upregulation as a driver of cellular replication and cell cycle checkpoint escape. (biomedcentral.com)
  • Next, they combined them with other mutations affecting cell cycle checkpoints or apoptosis until they hit upon the combinations that are sufficient to initiate tumorigenesis or to generate certain types of tumors. (rdworldonline.com)
  • disorder have mutations in both copies of the ATM gene in each cell. (diff.org)
  • When mammalian cell experiences DNA damage, it activates checkpoint mechanisms to stall the progression of cell cycle and DNA replication. (nii.res.in)
  • Summing up, we are trying to understand the mechanisms by which microRNAs regulate mammalian cell cycle and DNA replication in normal and pathological conditions. (nii.res.in)
  • Studies the molecular mechanisms of DNA replication, recombination, and repair. (rockefeller.edu)
  • In mammalian cells the inactivation of these surveillance mechanisms can lead to cancer. (unt.edu)
  • In the course of my postdoctoral work I came to appreciate the beauty and sophistication of the intricate regulatory mechanisms that drive cell cycle progression in general, and chromosome segregation in particular, and I decided to continue this line of research in my own lab. (unt.edu)
  • consequently cells have evolved a variety of mechanisms to repair double-strand breaks (DSBs). (brandeis.edu)
  • [ 6 ] These events lead the cancer cell to escape normal cell growth and control mechanisms, to avoid system control mechanisms (ie, immunologic surveillance), and to establish a nutrient supply. (medscape.com)
  • EXPERIMENTAL PROCEDURES Cell Culture and Synchronization HEK293T T98G and HeLa cells were produced in Dulbecco's altered Eagle's medium with 8% fetal calf serum. (exposed-skin-care.net)
  • His laboratory also contributed to understanding how replication origins are regulated by checkpoint kinases in response to DNA damage. (royalsociety.org)
  • Once a T cell is activated through its T-cell receptor, downstream T-cell receptor signaling through Src kinases results in tyrosine phosphorylation of CTLA4 and the uncoupling of CTLA4 from AP50, allowing its surface expression, which peaks at 48 h after activation. (snmjournals.org)
  • Cyclins are central engines of cell cycle progression in conjunction with cyclin-dependent kinases (CDKs). (ox.ac.uk)
  • Checkpoint control kinases is a term used to describe a group of enzymes that regulate progression of a cell through the cell cycle. (tocris.com)
  • Checkpoint control kinases function to halt the cell cycle at these critical points. (tocris.com)
  • Tocris offers the following scientific literature for Checkpoint Control Kinases to showcase our products. (tocris.com)
  • Given the previously reported role of DUSP4 as a p53 target, a potential cell cycle checkpoint, and in mediating senescence downstream of replication stress, we hypothesized that DUSP4 may be a critical oncogenic driver in breast cancer. (biomedcentral.com)
  • Among the different cyclins controlling cell cycle progression, cyclin F does not partner with a CDK, but instead forms via its F-box domain an SCF (Skp1-Cul1-F-box)-type E3 ubiquitin ligase module. (ox.ac.uk)
  • Although various substrates of cyclin F have been identified, the vulnerabilities of cells lacking cyclin F are not known. (ox.ac.uk)
  • Thus, we assessed viability of cells lacking cyclin F upon challenging them with more than 180 different kinase inhibitors. (ox.ac.uk)
  • Replication catastrophe depends on accumulation of the transcription factor E2F1 in cyclin F-depleted cells. (ox.ac.uk)
  • Replication of DNA is initiated at multiple sites along the genome, known as replication origins, which form bidirectional replication forks. (bmj.com)
  • The BRCA2 R3052W mutated protein exacerbates genome instability, is unable to rescue homology-directed repair, and fails to complement cell survival following exposure to PARP inhibitors and crosslinking drugs. (frontiersin.org)
  • Therefore, we are trying to understand the independent mechanism by which mammalian cells effectively inhibit the replication machinery during stress preventing it from drifting towards a catastrophic path of genomic instability. (nii.res.in)
  • Our research focus is to understand the structure and function of unusual DNA sequences in living cells, and how these sequences cause genome instability and lead to human diseases. (virginia.edu)
  • If cells containing damaged DNA were to divide, the errors would be transmitted to daughter cells, generating genomic instability and resulting in tumorigenesis or apoptosis . (tocris.com)
  • The study also demonstrates that mice with a high degree of chromosomal instability and defective programmed cell death (apoptosis), two hallmarks of cancer, rarely develop tumors. (rdworldonline.com)
  • John Diffley is known for his elegant use of genetics, biochemistry, molecular and cellular biology to elaborate the events that occur at origins of eukaryotic DNA replication throughout the cell cycle. (royalsociety.org)
  • Furthermore SNF2H is certainly apparently recruited GSK 525762A towards the Epstein-Barr pathogen origins of plasmid replication ((37). (exposed-skin-care.net)
  • Within this research the hypothesis was explored that SNF2H protein might are likely involved in the excitement of MCM launching onto mobile replication origins which the Cdt1-SNF2H conversation is usually important in this context. (exposed-skin-care.net)
  • On the basis of the data obtained we propose that SNF2H promotes MCM loading at cellular replication origins through conversation with Cdt1. (exposed-skin-care.net)
  • The activation of replication checkpoint may slow down DNA replication and improve DNA replication fidelity, which increases the maintenance of genomic stability and counteracts carcinogenesis. (nih.gov)
  • Feng et al established in 2008 that approximately 80% of Merkel cell carcinomas in the Northern hemisphere occur after genomic integration by a ubiquitous skin commensal virus, Merkel cell polyoma virus (MCPyV). (medscape.com)
  • via conversation with Cdt1 in human cells. (exposed-skin-care.net)
  • Because efficient loading of excess MCM complexes is usually thought to be required for cells to tolerate replication tension Cdt1- and SNF2H-mediated advertising of MCM loading could be biologically relevant for the legislation of DNA replication. (exposed-skin-care.net)
  • In this respect HBO1 (a MYST family members histone acetyltransferase that binds to ORC) originally determined through its physical connections with individual ORC1 (27) was lately discovered to associate with replication roots through relationship with Cdt1 also to enhance licensing and DNA replication through its acetylation activity GSK 525762A (28-30). (exposed-skin-care.net)
  • In addition, CDC6 overexpression in primary cells may promote DNA hyper-replication and induce a senescence response similar to that caused by oncogene activation. (wikipedia.org)
  • Ongoing projects include examining the chromatin structure of cancer-specific fragile sites, and their involvement in DNA replication/cell cycle checkpoints, and investigating the mechanism of RET/PTC rearrangement. (virginia.edu)
  • The first is a stochastic model of the progression of cell cycle states, which is applied to experimental data for two synchronized isogenic MMR + and MMR − colon cancer cell lines treated with and without IUdR. (aacrjournals.org)
  • I am a senior lecturer in Cell Bilogy and a member of the plant biology group. (brookes.ac.uk)
  • Previous to this I completed my BSc in Cell and Human Biology here at Oxford Brookes University. (brookes.ac.uk)
  • For a century, the nucleus has been the focus of extensive investigations in cell biology. (brookes.ac.uk)
  • Petra Levin, the George William and Irene Koechig Freiberg Professor of Biology in Arts & Sciences at Washington University, an author of the new paper, has a keen interest in single-cell biology. (scitechdaily.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)
  • Despite this defect, the mutant cells progress into the meiotic program and undergo lethal segregation of unreplicated DNA suggesting that they fail to activate a checkpoint that restrains meiotic M phase until DNA replication is complete. (ox.ac.uk)
  • Although cells that lack clb5 and clb6 are unable to activate the meiotic DNA replication checkpoint, they do possess an intact DNA damage checkpoint which can restrain chromosome segregation in the face of DNA damage. (ox.ac.uk)
  • The cytotoxic T lymphocyte-associated antigen 4 (CTLA4) is a coinhibitory activation-induced surface receptor on T cells that functions as a major negative regulator of anti-self-immune responses. (snmjournals.org)
  • Finally, we showed that ssDNA lesions are converted to toxic DSBs in cells lacking functional ataxia telangiectasia mutated (ATM), likely due to failure to form 53BP1 bodies and/or a role for ATM in SSB repair or fork protection [ 14 ]. (nature.com)
  • We found that 5-ASA at concentrations between 10 and 40 mmol/L affects cell cycle progression by inducing cells to accumulate in the S phase. (nih.gov)
  • Our data demonstrate that 5-ASA causes cells to reversibly accumulate in S phase and activate an ATR-dependent checkpoint. (nih.gov)
  • Research from O'Donnell's lab has provided an overview of how the replication machine, or replisome, functions in Escherichia coli , yeast, and humans. (rockefeller.edu)
  • From experiments in the 1870s to research more than 100 years later, scientists have made fascinating discoveries about the complex series of events that allow the cells in plants and animals, including humans, to grow and sustain life. (visionlearning.com)
  • Overexpression of R3052W in DLD1 parental BRCA2 wild-type cells confers sensitivity to MMC DNA damage. (frontiersin.org)
  • Higher DNA damage, p53 overexpression, greater delay in cell kinetics and lower GSH levels in peripheral blood lymphocytes have been demonstrated in heavy RAN chewers than in non-chewers [ 8 ]. (biomedcentral.com)
  • The team employs strategies such as super resolution microscopy to observe individual replisomes in real time during DNA replication in living cells, and cryo-electron microscopy of DNA-replisome and other replisome-associated complexes. (rockefeller.edu)
  • A protein found in DNA replication complexes is also essential for ribosome biosynthesis, according to new results from Yi-Chieh Du and Bruce Stillman (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY). (rupress.org)
  • Selecting catalytic ATPase subunits coupled with various other complicated elements defines the function of the complexes in a variety of nuclear occasions including transcription DNA replication and DNA fix. (exposed-skin-care.net)
  • Since it is well recognized that errors in the centrosome duplication contribute to tumorigenesis we are interested in determining the role of replication factors in preventing aneuploidy. (nii.res.in)
  • We found that Dusp4 loss alone is insufficient in mediating tumorigenesis, but alternatively converges with loss in Trp53 and MYC amplification to induce tumorigenesis primarily through chromosome 5 amplification, which specifically upregulates Dbf4 , a cell cycle gene that promotes cellular replication by mediating cell cycle checkpoint escape. (biomedcentral.com)
  • This is the multihit theory of tumorigenesis, in which a series of multiple triggering events in the genetic and cellular makeup of a cell ultimately cause cancer. (medscape.com)
  • CLB5 and CLB6 are required for premeiotic DNA replication and activation of the meiotic S/M checkpoint. (ox.ac.uk)
  • We report here that cells undergoing meiotic development also require Clb dependent CDK activity for DNA replication. (ox.ac.uk)
  • We conclude that CLB5 and CLB6 are essential for premeiotic DNA replication and, consequently, for activation of a meiotic DNA replication checkpoint. (ox.ac.uk)
  • To this end we have expressed the site-specific HO endonuclease in meiotic cells so that we can compare recombination events at the same loci where we have used HO to stimulate recombination in mitotic cells. (brandeis.edu)
  • We find that nontransformed cells undergo a TP53-dependent growth arrest and activate interferon signaling in response to LINE-1. (nih.gov)
  • DNA is loaded through the 9-1-1 DNA checkpoint clamp in the opposite direction of the PCNA clamp. (rockefeller.edu)
  • Immunohistochemical analysis of paraffin embedded Jurkat cell pellets, untreated (left) or etoposide-treated (right), using Phospho-Histone H3 (Ser10) Antibody, PCNA (PC10) Mouse mAb, Cleaved Caspase-3 (Asp175) Antibody and Survivin (71G4B7E) Rabbit mAb. (cellsignal.com)
  • These effects resulted in significant accumulation of unreplicated single-stranded DNA and increased cell death, indicative of replication catastrophe. (nature.com)
  • Our findings pave the way for patient selection in the clinical use of checkpoint inhibitors. (ox.ac.uk)
  • (B) Western blot of total cellular lysates from DLD-1 BRCA2 −/− cells stably transfected with full-length BRCA2 cDNA constructs: BRCA2 Wild Type (WT) and BRCA2 R3052W (1 and 2 correspond to two independent clones). (frontiersin.org)
  • (F) Western blot of total cellular lysates from DLD-1 parental cells (these cells express a wild-type allele of BRCA2) stably transfected with R3052W (3 and 5 correspond to two independent clones) full-length 2XMBP-BRCA2 cDNA constructs. (frontiersin.org)
  • Cellular studies show the replisome is intimately involved with the inheritance of epigenetic information and cell fate, and the O'Donnell lab is working to understand the mechanistic details of these processes. (rockefeller.edu)
  • Replication fork activation is enabled by a single-stranded DNA gate in CMG helicase. (rockefeller.edu)
  • Most plant and animal cells replicate by splitting into two identical daughter cells. (visionlearning.com)
  • Aberrations in microRNA activity has been linked to loss of cell cycle and replication control and this has led to oncogenic functions (thereby called oncomirs) being ascribed to them. (nii.res.in)
  • control the rate at which cells grow and divide. (diff.org)
  • DNA polymerase ε (Pol ε) is involved in DNA replication, repair, and cell-cycle checkpoint control in eukaryotic cells. (webnode.page)
  • In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. (affbiotech.com)
  • More recently I've developed an interest in nuclear structure, the determinants of which are largely unknown, and yet it is an integral part of many biological processes, such as gene expression, DNA replication and DNA repair. (unt.edu)
  • The BRCA2 R3052W mutation fails to complement chemotherapeutic sensitivity and homology-directed repair functions in BRCA2 knockout cells. (frontiersin.org)
  • These checkpoints may stop the cell cycle after DNA damage, loss of DNA replication or disruption of the mitotic spindle, in order for repair processes to take place. (tocris.com)
  • Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the stages of the cell cycle and DNA repair. (tocris.com)
  • If the cell detects errors in any of these phases, cell growth is halted and highly complex DNA repair processes are triggered. (rdworldonline.com)
  • Previous studies in our laboratory have described increased and preferential radiosensitization of mismatch repair-deficient (MMR − ) HCT116 colon cancer cells with 5-iododeoxyuridine (IUdR). (aacrjournals.org)
  • This gene product is involved in cell cycle progression, p53-mediated apoptosis, transcription activator of several other oncogenes [ 4 ] and DNA repair [ 5 ]. (biomedcentral.com)
  • We have shown that there are differences between this repair-induced replication fork and the normal replication process, but there is much more work to do. (brandeis.edu)
  • Because of its central role in cell division and DNA repair, the ATM protein is of great interest in cancer research. (diff.org)
  • Catastrophic genetic damage can occur if cells progress to the next phase of the cell cycle before the previous phase is properly completed. (tocris.com)
  • CDC6 is normally present at high levels during the G1 phase of the cell cycle. (wikipedia.org)
  • Yph1p levels were high in proliferating cells, but declined as cells entered the quiescent phase. (rupress.org)
  • Checkpoint systems allow the accurate execution of each cell-cycle phase. (ox.ac.uk)
  • Cancer cells, particularly those arising from the bone marrow or lymphatic system, may have a short generation time, and there usually are a smaller percentage of cells in G0 (resting phase). (msdmanuals.com)
  • Some drugs work only during a specific phase of the cell cycle, requiring prolonged administration to catch dividing cells during the phase of maximal sensitivity. (msdmanuals.com)
  • Epidemiologic, animal, and laboratory studies suggest that 5-amino-salicylic acid (5-ASA) protects from the development of CRC by altering cell cycle progression and by inducing apoptosis. (nih.gov)
  • We tested the role of whole-body molecular imaging in patients with advanced melanoma receiving the CTLA4-blocking antibody tremelimumab, allowing the analysis of changes in glucose metabolism using the PET probe 18 F-FDG and cell replication with the PET probe 3′-deoxy-3′- 18 F-fluorothymidine ( 18 F-FLT). (snmjournals.org)
  • Most naïve T cells do not express surface CTLA4 because of its binding to AP50, a subunit of the clathrin adaptor AP-2 protein ( 2 ). (snmjournals.org)
  • Cell surface CTLA4 has 100-1,000 times higher affinity for the costimulatory molecules expressed by antigen-presenting cells, thereby efficiently competing with the positive costimulatory receptor CD28 ( 1 ). (snmjournals.org)
  • The engagement of CTLA4 by costimulatory molecules results in decreased T-cell receptor signaling, interleukin 2 transcription ( 3 ), and cell cycle arrest at the G1 stage, with the final result of inducing T-cell anergy ( 4 , 5 ). (snmjournals.org)
  • The most consistent effects in peripheral blood cells after administering anti-CTLA4 antibodies have been limited to marginal increases in the surface expression of nonspecific activation markers predominantly on CD4+ T lymphocytes ( 16 - 18 ). (snmjournals.org)
  • STARD14 was negatively associated with the infiltration of CD8+T cells, while positively with CCL28 and immune checkpoints, including CTLA4 as well as PD-L2. (medsci.org)
  • Recombination between homologous sequences is a fundamentally important process both in meiosis and in mitotic cells. (brandeis.edu)
  • Using synchronized cells undergoing recombination that is initiated at a specific site on a chromosome by an inducible endonuclease, we use physical monitoring techniques (Southern blots, PCR analysis) to follow the sequence of molecular events that occur in real time. (brandeis.edu)