Phase dna damage checkpoint defects. Medical search. Frequent questions

Eco1 interacts with many proteins directly involved in DNA replication, including the processivity clamp PCNA, clamp loader subunits, and a DNA helicase. (wikipedia.org)
8 , 9 The protein is a member of a novel family of large proteins, which show sequence homology to the catalytic domain of phosphatidylinositol 3 kinase, 3 and are implicated in cell cycle regulation, signal transduction, and the response to DNA damage. (bmj.com)
4 , 10 There is evidence to suggest that these proteins respond to DNA damage by phosphorylating one or more substrates, including p53, c-Abl, and replication protein A (RPA), to recruit proteins to regions of DNA repair and/or to activate radiation signal transduction pathways. (bmj.com)
Studies in yeast and animals indicate that ASF1 proteins play important roles in various chromatin-based processes, including gene transcription, DNA replication and repair. (nih.gov)
Recent breakthroughs have uncovered more and more DNA replication licensing machinery proteins (ORC, Cdc6, Cdt1, geminin, etc.) functioning in other cell cycle events, including centrosome replication, mitotic events, transcription and so on. (intechopen.com)
For instance, SMC proteins (COOH-terminal fragments) are capable of binding DNA in the absence of Mcd1p. (rupress.org)
This is accompanied by DNA double-strand break (DSB) induction and recruitment of the DNA repair proteins replication protein A, Rad51, and 53BP1 to damaged regions. (rupress.org)
As a DSB related proteins considerably appear the possibilities for targeting DNA repair defective tumors or hyperactive DNA repair tumors. (bmbreports.org)
J-H Lee et al also have provided the first evidence showing that PIG3 is closely associated with the induction and maintenance of the phosphorylation of H2AX and some other DDR proteins after DNA damage induced by NCS ( 8 ). (ijbs.com)
and Other Mitotic Proteins Are Decreased in DNA-Dependent Protein Kinase Catalytic Subunit-Deficient Cells and Rescued by Inhibition of the Anaphase-Promoting Complex/Cyclosome with proTAME but Not Apcin. (xenbase.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)
During NHEJ, once a DSB is formed the broken ends are bound by Ku proteins (ku70 and ku80), which form a heterodimer and insulate the DNA ends from nucleolytic erosion [ 11 , 12 ]. (springeropen.com)
The Ku proteins foster direct ligation of the broken DNA ends by the specialized ligase complex Dnl4-Lif1 [ 12 ]. (springeropen.com)
Here, the fusion proteins MLL-AF4 (MA4) and AF4-MLL (A4M) were CRISPR/Cas9-genome edited in the AAVS1 locus of HEK293 cells as a model to study MLL fusion-mediated DNA-DSB formation/repair. (ibecbarcelona.eu)

In general, cohesion is established during S phase as DNA is replicated, and is lost when chromosomes segregate during mitosis and meiosis. (wikipedia.org)
The pre-replication complex (pre-RC) assembly or the DNA replication licensing is the first step in DNA replication initiation, characterized by the sequential recruitment of ORCs, Cdc6, Cdt1 and MCMs to the DNA replication origins to form the pre-RC at the end of mitosis ( Bell and Dutta 2002 ). (intechopen.com)
The G 2 gap phase further separates S-phase from mitosis, allowing for continued cell growth and maturation before cell division. (rupress.org)
Thus, the products of chromosome replication (sister chromatids) generated during S-phase must be identified over time until mitosis when sisters associate with the mitotic spindle and segregate away from each other into the newly forming daughter cells. (rupress.org)
Upon treatment with Plk1 inhibitors, p53 in tumor cells is activated and induces strong apoptosis, whereas tumor cells with inactive p53 arrest in mitosis with DNA damage. (oncotarget.com)
Plk1 is mainly expressed during the late G2 and M phase, where it regulates various stages of mitosis [ 2 , 7 ]. (oncotarget.com)

Embryos lacking E4F die at the peri-implantation stage, while in vitro-cultured E4F(-/-) blastocysts exhibit defects in mitotic progression, chromosomal missegregation, and increased apoptosis. (cnrs.fr)
For instance, DNA replication and DNA damage checkpoints delay cell cycle progression until each chromosome is fully replicated and physically intact. (rupress.org)
Tumor initiation, progression, and evolution are often rooted in the malfunctioning of the checkpoints securing genome integrity. (biomedcentral.com)
Furthermore, we find that SET8 interacts with proliferating cell nuclear antigen through a conserved motif, and SET8 is required for DNA replication fork progression. (rupress.org)
PIG3 knockdown led to an abnormal DNA damage response, including decreased IR-induced phosphorylation of H2AX, Chk1, Chk2 and Kap-1 as well as a prolonged G2-M arrest and aberrant mitotic progression. (ijbs.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)
PARP inhibitors can trap the PARP-1 protein at a single-stranded break/DNA lesion and disrupt its catalytic cycle, ultimately leading to replication fork progression and consequent double-strand breaks. (biomedcentral.com)

Maintaining the genomic machinery is not a flawless process: DNA damage, genotoxic stresses, and defects in the repair pathways can all contribute to destabilizing the complex molecular networks keeping the genome intact. (biomedcentral.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)
The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. (helixlabs.ai)
The two most commonly used pathways to repair DSBs in higher eukaryotes include non-homologous end joining (NHEJ) and homologous recombination (HR). NHEJ is considered to be error-prone, intrinsically mutagenic quick fix remedy to seal together the broken DNA ends and restart replication. (springeropen.com)
DNA double strand break repair (DSBR) pathways are generally classified based on whether sequence homology is used to join the broken DNA ends. (springeropen.com)

DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. (bmbreports.org)
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)
Circulating tumor DNA association with residual cancer burden after neoadjuvant chemotherapy in triple-negative breast cancer in TBCRC 030. (cdc.gov)

RIF1 inhibition resulted in radiosensitivity and a defect in the intra-S-phase checkpoint. (wikisequences.org)
PIG3 knockdown can suppress intra-S phase and G2/M checkpoints ( 8 ). (ijbs.com)

CLB5 and CLB6 are required for premeiotic DNA replication and activation of the meiotic S/M checkpoint. (ox.ac.uk)

All of these defects are associated with impaired activation of the ATR/CHK1 pathway. (nature.com)
SET8 depletion causes DNA damage specifically during replication, which induces a Chk1-mediated S-phase checkpoint. (rupress.org)
Here, we demonstrate that the S phase checkpoint protein CHK1 is maintained in a low phosphorylation state in Spi1/PU.1-overexpressing cells and provide evidence that this is not due to negative control of its primary kinase ATR. (oncotarget.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)

Consistent with these observations, we found that E4F localizes to the mitotic spindle during the M phase of early embryos. (cnrs.fr)
Initiation of DNA replication during the mitotic cell cycle requires the activation of a cyclin-dependent protein kinase (CDK). (ox.ac.uk)
In addition, compared to the mono-treatment, combination of Polo-like kinase 1 inhibition with anti-mitotic or DNA damaging agents boosts more severe mitotic defects, effectually triggers apoptosis and strongly inhibits proliferation of cancer cells with functional p53. (oncotarget.com)
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)

Furthermore, the Atasf1ab-triggered replication fork stalling constitutively activates the DNA damage checkpoint and repair genes, including ATM, ATR, PARP1 and PARP2 as well as several genes of the homologous recombination (HR) pathway but not genes of the non-homologous end joining (NHEJ) pathway. (nih.gov)
This may suggest that caspase-2 activates a non-canonical replication checkpoint to facilitate DNA repair. (nature.com)

We propose a model where caspase-2 regulates the cell cycle and protects DNA replication forks to prevent DNA damage accrual in a pathway distinct from its apoptotic role. (nature.com)
Consistent with our evidence that caspase-2 regulates a replication checkpoint, the chromosomal aberrations detected in caspase-2-deficient cells are not repaired before metaphase. (nature.com)
Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. (helixlabs.ai)

The precise regulations of pre-RC protein levels and assembly are effective ways to prevent reassembly of de novo MCM2-7 onto the replicated origins to re-license and re-replicate the genomic DNA in the subsequent phases of the same cell cycle ( Figure 1) . (intechopen.com)
Finally, codepletion of Rad51, an important homologous recombination repair protein, abrogates the DNA damage after SET8 depletion. (rupress.org)
Notably, PIG3 knockdown resulted in a striking depression of cellular DNA-PKcs protein level, and was accompanied by a downregulation of ATM. (ijbs.com)
This negative regulation of DNA-PKcs by depleting PIG3 seemed to take place at the translational level but not at the levels of transcription or protein degradation. (ijbs.com)
However, a compensatory feedback of increased mRNA expression of DNA-PKcs was formed in PIG3-depleted cells after a few passages or cell cycles of subculture, which led the recovery of the DNA-PKcs protein level and the consequent recovered efficiency of the DNA damage response. (ijbs.com)
Protein phosphatase 1 and phosphatase 1 nuclear targeting subunit-dependent regulation of DNA-dependent protein kinase and non-homologous end joining. (xenbase.org)
E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. (helixlabs.ai)

The B-type cyclins Clb5 and Clb6 are the primary activators of the S phase function of the budding yeast CDK Cdc28. (ox.ac.uk)

Homologous recombination is the main mechanism to repair DNA lesions that block replication forks and fill ssDNA gaps left behind the fork [11]. (nature.com)
DNA DSB repair signaling contributes to general mechanism for various types of lesions in diverse cell cycle phases. (bmbreports.org)
How do cells sense DNA lesions? (xenbase.org)
Importantly, alkylating agents induce DNA damage at different genomic sites, which subsequently leads to lethal and/or mutagenic DNA base lesions. (frontiersin.org)
In comparison, the SN2 agent methyl methane sulfonate (MMS) induces N 1 -methyladenine (m 1 A) and N 3 -methylcytosine (m 3 C) lesions, preferably in single-stranded DNA (ssDNA). (frontiersin.org)

Sister chromatid cohesion refers to the process by which sister chromatids are paired and held together during certain phases of the cell cycle. (wikipedia.org)
Though cohesin can associate with chromatin earlier in the cell cycle, cohesion is established during S phase. (wikipedia.org)
Tying establishment to DNA replication allows the cell to institute cohesion as soon as the sister chromatids are formed. (wikipedia.org)
Members of this kinase family have been shown to function in DNA repair and cell cycle checkpoint control following DNA damage. (bmj.com)
The Atasf1ab mutant plants exhibit cell number reduction, S-phase delay/arrest, and reduced polyploidy levels. (nih.gov)
In this chapter, we mainly discuss the coordination regulations between DNA replication initiation and other cell cycle events that ensure genomic integrity. (intechopen.com)
DNA replication occurs once and only once per cell cycle mainly regulated by DNA replication initiation factors in eukaryotic cells. (intechopen.com)
2004) found that human RIF1 did not accumulate at functional telomeres, but localized to dysfunctional telomeres and to telomeric DNA clusters in human ALT (alternative lengthening of telomeres) cell lines, which maintain telomeric DNA in the absence of telomerase. (wikisequences.org)
In our paper published in Oncogene [6], we show that caspase-2 plays an essential role in regulating normal cell division by protecting DNA replication forks from replication stress. (nature.com)
therefore, we overexpressed Bcl-X L to distinguish caspase-2's role in cell division and DNA protection from its role in apoptosis. (nature.com)
In contrast, while caspase-2-deficiency led to an increased proportion of S-phase cells and a progressive decrease in the proportion of G1-phase cells following treatment with arresting concentrations of the DNA damaging agent camptothecin and increased DNA damage following S-phase arrest, overexpression of Bcl-X L did not change the cell cycle profiles or the amount of DNA damage. (nature.com)
While other groups have demonstrated non-apoptotic roles for caspase-2 in DNA repair, cell cycle arrest [2], this is the first demonstration that these roles are regulated by a distinct pathway to apoptosis. (nature.com)
We show that small interfering RNA inhibition of SET8 expression leads to decreased cell proliferation and accumulation of cells in S phase. (rupress.org)
Five members of the Plk family have been discovered in humans and these serine/threonine kinases have emerged as key players by performing crucial functions in the cell cycle, DNA damage response and neuron biology [ 2 - 6 ]. (oncotarget.com)
Plk3 is expressed throughout the cell cycle and involved in cellular response to DNA damage [ 9 ]. (oncotarget.com)
In the present study, the potential mechanism of PIG3 participation in the DNA damage response induced by ionizing radiation (IR) was investigated in multiple cell lines with depleted expression of PIG3 transiently or stably by the small interference RNA and lentivirus-mediated shRNA expression strategies. (ijbs.com)
The DNA double-strand break (DSB) is considered to be the most severe type of DNA damage induced by ionizing radiation, and this form of DNA damage must be repaired immediately to prevent cell death. (ijbs.com)
In particular, the loss of ALKBH6 in human pancreatic cancer cells increases alkylating agent-induced DNA damage and significantly decreases cell survival. (frontiersin.org)
Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. (helixlabs.ai)
The current version of the model gives predictions of the yields and sizes of translocations, dicentrics, rings, and more complex-type aberrations formed in the G 0 /G 1 cell cycle phase during the first cell division after irradiation. (bioone.org)
The Forsburg lab uses a mixture of classical genetics, molecular biology, and state-of-the-art microscopy to investigate how defects in replication contribute to genome instability during normal cell growth and during the differentiation process of meiosis. (usc.edu)
Treatment with etoposide consistently induced cell cycle arrest in S/G2/M independent of MA4/A4M expression, revealing a proper activation of the DNA damage checkpoints. (ibecbarcelona.eu)

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)

J-H Lee et al extensively investigated the participation of PIG3 in DNA damage checkpoints after UV irradiation or after treatment using the radiomimetic drug neocarzinostatin (NCS) ( 8 ). (ijbs.com)

We show that caspase-2 protects cells from a range of S-phase-related defects, including delayed exit from S-phase, increased stalled replication forks, increased new replication origins, and decreased repair of S-phase-associated chromosomal aberrations [6]. (nature.com)
Caspase-2-deficient cells show a significantly higher percentage of S-phase-associated chromosomal aberrations. (nature.com)
A previously developed DNA-fragmentation model for high- and low-LET radiation called the NASARadiationTrackImage model was enhanced to simulate a stochastic process of the formation of chromosomal aberrations from DNA fragments. (bioone.org)

Specifically, we find that if JMJD1B is not present, chromatin assembly defects and DNA damage are observed. (biomedcentral.com)

Histone synthesis is tightly coupled to DNA replication and peaks during the G1/S phase transition to account for doubling the genome. (biomedcentral.com)
Outside S-phase a histone pool is maintained in case of unanticipated changes to histone demand, such as DNA damage [ 9 ]. (biomedcentral.com)
Theprotein binds to specific DNA sequences, and recruits a histone deacetylase to regulate geneexpression. (moonphase2018.com)

This indicates a role distinct from caspase-2's reported role in inducing apoptosis to remove damaged or aneuploid cells [7][8]. (nature.com)
cells have been found in association with cytotrophoblasts and present a periarteriolar attention around maternal bloodstream in metrial gland and decidua.In the mouse, it was described that after mid gestation some of these cells introduced DNA fragmentation, binucleation, indicating a failure in cytokinesis and enlargement of the cytoplasm accompanied by degranulation suggesting that these cells undergo apoptosis and/or necrosis. (pimpathway.com)

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)
In eukaryotes, DNA replication is separated in time from chromosome segregation. (rupress.org)

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)
Recent innovations have helped to develop prescription drugs against certain prostate cancer types, showing gene alterations that prevent the repair of damaged DNA or activate the body's anti-cancer natural immune defense. (mdpi.com)

The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. (bmbreports.org)
Data from other trials suggest there may be improved activity in men with DNA damage repair (DDR) mutations treated with checkpoint inhibitors. (bmj.com)

We encourage submissions of work that expands the mechanistic knowledge of DNA damage, repair, integrity, and stability as well as research that translates these concepts to ultimately target cancer at the bedside. (biomedcentral.com)
In this Collection, guest edited by Christopher Lord and Timothy Yap, we aim to highlight insights that expand upon our mechanistic knowledge of DNA damage, repair, integrity, and stability as well as research that leverages these concepts to ultimately target cancer at the bedside. (biomedcentral.com)
DNA double strand breaks (DSBs) result as a consequence of the disassembly of the DNA double helix leading to the disruption of the stability of the genome. (springeropen.com)
Forsburg takes a holistic approach to studying how DNA replication stress contributes to genome stability. (usc.edu)

DNA damage, from cellular metabolism or exogenous sources, and unscheduled oncogene expression both lead to replicative stress and represent major sources of genetic instability. (oncotarget.com)
Here, we tested whether ALKBH6 plays a significant role in preventing alkylating DNA damage and decreasing genomic instability in pancreatic cancer cells. (frontiersin.org)

promotes DNA double-strand break repair in distinct chromosomal contexts. (xenbase.org)

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)
DSBs not only ensue from normal cellular metabolism, in the form of reactive oxygen species that can oxidize DNA bases [ 1 , 2 ], but can also be generated during physiological processes like chromosome replication, meiotic recombination and DNA replication transcription collision [ 3 - 7 ]. (springeropen.com)

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)

Defects in DNA double-strand break (DSB) repair signaling permit cancer cells to accumulate genomic alterations that confer their aggressive phenotype. (bmbreports.org)
Phase II Trial of Olaparib in Patients With Metastatic Urothelial Cancer Harboring DNA Damage Response Gene Alterations. (cdc.gov)

Diploid clb5/clb5 clb6/clb6 mutants are unable to perform premeiotic DNA replication. (ox.ac.uk)

Current standard of care involves maximal surgical resection followed by concurrent therapy with radiation and the DNA alkylating agent temozolomide. (bmj.com)

Loss-of-function of either AtASF1A or AtASF1B did not show obvious defects, whereas simultaneous knockdown of both genes in the double mutant Atasf1ab drastically inhibited plant growth and caused abnormal vegetative and reproductive organ development. (nih.gov)

They noted that this pattern of telomere association is typical of DNA damage response factors. (wikisequences.org)
After induction of double-strand breaks in ALT cells, RIF1 formed foci that colocalized with other DNA damage response factors. (wikisequences.org)
Plk2 is an immediate early response gene and is expressed in early G1, where it controls the entry into S phase [ 8 ]. (oncotarget.com)
DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. (bmbreports.org)
The p53-inducible gene 3 (PIG3) recently has been reported to be a new player in DNA damage signaling and response, but the crucial mechanism remains unclear. (ijbs.com)
Recently, PIG3 has been shown to participate in the DNA damage response as well ( 6 - 8 ). (ijbs.com)
This was the first evidence suggesting the involvement of PIG3 in the IR-induced DNA damage response. (ijbs.com)
promotes DNA damage response pathway from a single-strand break. (xenbase.org)
is a direct negative regulator of the DNA-damage response. (xenbase.org)
Specifically, the concepts of tumour heterogeneity, oncogene addiction, non-oncogene addiction, tumour initiating cells, tumour microenvironment, non-coding sequences and DNA damage response will be reviewed. (bmj.com)
Involved in transcriptional regulation of P21 in response to DNA damage. (helixlabs.ai)
They are a direct consequence of mis-repaired DNA double strand breaks (DNA-DSBs) due to defects in the DNA damage response associated with exposure to topoisomerase-II poisons such as etoposide. (ibecbarcelona.eu)

Selective up-regulation of expression of a subset of genes, including those involved in S-phase checkpoints and the CYCB1;1 gene at the G₂-to-M transition, was observed in Atasf1ab. (nih.gov)
In spite of the activation of repair genes, an increased level of DNA damage was detected in Atasf1ab, suggesting that defects in the mutant largely exceed the available capacity of the repair machinery. (nih.gov)
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)
We list the DNA repair genes and related E3 ligases. (bmbreports.org)

Nevertheless, tumors depend on residual DNA repair abilities to survive the DNA damage induced by genotoxic stress. (bmbreports.org)

These results provide a new insight into the mechanism of PIG3's functioning in DNA damage signaling and the regulation network of cellular DNA-PKcs expression homeostasis. (ijbs.com)

2004) concluded that RIF1 contributes to ATM-mediated protection against DNA damage. (wikisequences.org)
How exactly caspase-2 contributes to DNA repair is unclear. (nature.com)
Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. (helixlabs.ai)

Decreased CAR expression may contribute to the maturation defect and altered migration of EP and thus their pathologic accumulation in the BM in MDS. (bvsalud.org)

Replication of DNA is initiated at multiple sites along the genome, known as replication origins, which form bidirectional replication forks. (bmj.com)

The DNA repair field is a vibrant one, and the stage is ripe for scrutinizing the potential treatment efficacy and future clinical applications of the pharmacological inhibitors of HR enzymes as mono- or combinatorial therapy regimes. (springeropen.com)
Background Checkpoint inhibitors have not been effective for prostate cancer as single agents. (bmj.com)

In combination with immune checkpoint blockade (ICB), epigenetic modification-targeted drugs are emerging as attractive cancer treatments. (biomedcentral.com)
However, cancer cells exploit these checkpoints to evade immune surveillance and suppress antitumor immune responses. (biomedcentral.com)
He is an Associate Professor in the Department for Investigational Cancer Therapeutics (Phase I Program), and the Department of Thoracic/Head and Neck Medical Oncology. (biomedcentral.com)
This is why only isolated DNA repair signaling is inactivated in cancer cells. (bmbreports.org)
The extremely low 5-year overall survival of patients is, in part, due to pancreatic cancer cells having several mechanisms of resistance to different chemotherapeutic treatments, one of which is their capacity to efficiently repair alkylating agent-induced DNA damage. (frontiersin.org)
Several alkylating agents are commonly used in chemotherapy but may induce DNA damage to cancer cells as well as normal cells. (frontiersin.org)
Defects in the processes that maintain the integrity of our genome contribute to cancer, birth defects, and other disorders. (usc.edu)
Pilot clinical trial and phenotypic analysis in chemotherapy-pretreated, metastatic triple-negative breast cancer patients treated with oral TAK-228 and TAK-117 (PIKTOR) to increase DNA damage repair deficiency followed by cisplatin and nab paclitaxel. (cdc.gov)

Recombination based mechanisms are crucial for both the repair and tolerance of DNA damage that vexes both strands of the double helix [ 9 ]. (springeropen.com)

These checkpoints act as molecular brakes on immune cells, preventing excessive activation and potential damage to healthy tissues. (biomedcentral.com)

In particular, certain types of ALKBH enzymes are dioxygenases that directly reverse DNA methylation damage via transfer of a methyl group from the DNA adduct onto α-ketoglutarate and release of metabolic products including succinate and formaldehyde. (frontiersin.org)

RIF1 inhibits resection involving CTIP (604124), BLM (604610), and EXO1 (606063), limits accumulation of BRCA1/BARD1 (601593) complexes at sites of DNA damage, and defines one of the mechanisms by which 53BP1 causes chromosomal abnormalities in BRCA1-deficient cells. (wikisequences.org)
Required for FANCD2 targeting to sites of DNA damage. (helixlabs.ai)

At mid-S phase, its expression clearly preceded the replication fork in pericentric heterochromatin. (wikisequences.org)
However, we did not observe any MDM2 cleavage or caspase-2-dependent p21 expression following exposure to DNA damage or replication stress. (nature.com)
Re-expression of PIG3 effectively rescued the depression of DNA-PKcs in PIG3-depleted cells. (ijbs.com)
Its expression peaks at late G1 phase and continues during G2 and M phases of thecell cycle. (moonphase2018.com)
Collectively, expression of MA4 or A4M does neither influence DNA signaling nor DNA-DSB repair. (ibecbarcelona.eu)

BARD1 germline variants induce haploinsufficiency and DNA repair defects in neuroblastoma. (cdc.gov)

His research focusses on targeted therapies for DNA repair defective cancers, synthetic lethality and drug resistant cancers. (biomedcentral.com)

We previously showed that constitutive overexpression of the oncogenic transcription factor Spi1/PU.1 leads to pre-leukemic cells that have a shortened S phase duration with an increased replication fork speed and increased mutability in the absence of DNA breaks. (oncotarget.com)
In G1 phase, cells have a single centrosome consisting of two centrioles joined by cohesion fibers. (biomedcentral.com)
At the single channel level, 6 reduces availability of LVA calcium DNA-dependent RNA polymerase programs HEK 293 cells were transiently transfected with Cav3. (mdmsignaling.com)
It has been suggested that MLL fusions render cells susceptible to additional chromosomal damage upon exposure to etoposide. (ibecbarcelona.eu)

to DNA double-strand breaks. (xenbase.org)
in regulation of DNA double strand break dynamics and repair. (xenbase.org)
3 Mbp) that are below the resolution limits of current cytogenetic analysis techniques, we present predictions of hypothesized small deletions that may be produced as a byproduct of properly repaired DNA double-strand breaks (DSB) by nonhomologous end-joining. (bioone.org)

Direct DNA repair comprises several types of DNA repair enzymes that reversibly remove alkyl groups from damaged DNA bases through oxidative dealkylation processes. (frontiersin.org)

Anatomy21

Organisms8

Diseases12

Chemicals and Drugs111

Analytical, Diagnostic and Therapeutic Techniques and Equipment18

Phenomena and Processes91

Information Science3

Health Care3

Proteins16

Mitosis6

Progression7

Pathways5

Tumor3

Intra-S-phase2

Required for premeiotic1

CHK14

Mitotic4

Activates2

Regulates3

Protein7

Budding yeast1

Lesions5

Cell22

Mismatch repair1

Irradiation1

Chromosomal aberrations3

Chromatin1

Histone3

Apoptosis2

Chromosome segregation2

Activate2

Mutations2

Stability4

Instability2

Double strand break repair1

Meiotic3

Inhibition1

Alterations2

Mutants1

Radiation1

Knockdown1

Response12

Genes4

Genotoxic1

Cellular1

Contributes3

Maturation1

Replication forks1

Inhibitors2

Cancer8

Recombination1

Activation1

Methylation1

Sites of DNA damage2

Expression5

Variants1

Repair defective1

Cells4

Strand3

Processes1