• Currently, no cancer therapies specifically disrupt ALT pathways.1 Lee Zou, PhD, and his team at the Massachusetts General Hospital Cancer Center investigated the molecules and genes that drive the ALT pathway and how new treatments might disrupt this process. (massgeneral.org)
  • However, while DNA repair is often deficient in tumors, many DNA repair genes such as MLH1 , MGMT , BRCA1, or ATM do not commonly bear somatic mutations. (nature.com)
  • This is exemplified in "BRCAness" - a gene expression signature that suggests a deficient homologous recombination (HR) pathway, even in the absence of deleterious genetic variants in the BRCA1/2 genes. (nature.com)
  • In each category, studies related to growth control genes, cell proliferation, apoptosis, DNA repair genes, antioxidant and drug detoxification genes, genes of drug metabolizing enzymes, tissue remodeling genes and genes of antibody-dependent cellular cytotoxicity were discussed separately. (researchsquare.com)
  • A phenotypic RNAi screen of 300 DNA repair genes was undertaken to assess DNA repair targeting in more detail. (oncotarget.com)
  • A ) Bar graphs showing the mean z-score and standard deviation of 3 individual siRNAs against core HR pathway genes. (oncotarget.com)
  • Polymorphisms in DNA repair genes and susceptibility to primary intracranial brain gliomas. (cdc.gov)
  • Homologous recombination deficiency (HRD) is a defining characteristic in BRCA-deficient breast tumors caused by genetic or epigenetic alterations in key pathway genes. (lu.se)
  • Although senataxin's role in cells is not completely understood, it appears to be involved in the production of proteins from genes (transcription), the processing of RNA molecules, and the repair of damaged DNA. (medlineplus.gov)
  • The total chromosomal content of a cell involves approximately 105 genes in a specialized macromolecule of deoxyribonucleic acid (DNA). (cdc.gov)
  • To reduce the risk of analyzing cell line- pathway can be divided into distinct stages based on the specific features, we used several representative cell lines for recombination status of the Ig genes and on the expression each of four major stages in B cell development: pro-B, pre-B, pattern of surface markers and the presence of intracellular proteins [1- 6]. (lu.se)
  • The current study aimed to advance our understanding of tirapazamine-induced lesions and the pathways involved in their repair. (aacrjournals.org)
  • Nitrous acid is formed as a byproduct in the stomach from dietary sources of nitrites and can lead to crosslink lesions in DNA through the conversion of amino groups in DNA to carbonyls. (wikipedia.org)
  • Dr. Karen Vasquez, Smithville, TX - Processing of site-specific DNA lesions by DNA repair and recombination pathways 1.1.2 VIDEOARCHIVES: INTERNET ACCESS (WORLDWIDE): To date 54 of these videoconferences have been archived and are available for viewing at your leisure on the internet. (bio.net)
  • PROJECT SUMMARY/ABSTRACT Alkylating agents in our environment from tobacco, pesticides, and produced during drinking water purification cause DNA lesions. (nih.gov)
  • These DNA lesions can cause replication fork stalling and lead to DNA double-strand breaks that are canonically repaired by the homologous recombination (HR) pathway. (nih.gov)
  • Replication forks stall at DNA lesions or as a result of an unfavorable replicative environment. (yeastgenome.org)
  • This process directs the repair of many DNA lesions in somatic cells and generates genetic variation in sperm and egg cells during meiosis. (cshlpress.com)
  • The SOSS complex associates with DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. (thermofisher.com)
  • Base excision repair (BER) is the predominant DNA damage repair pathway for the processing of small base lesions, derived from oxidation and alkylation damages. (kegg.jp)
  • The planar compound links to nucleobases through water displacement of one or both of its chloride groups, allowing cisplatin to form monoadducts to DNA or RNA, intrastrand DNA crosslinks, interstrand DNA crosslinks, and DNA-protein crosslinks. (wikipedia.org)
  • We have shown that the invasion of DNA strands into a donor template region requires the action of the chromatin remodeling protein Rad54 that enables the recombination machinery to gain access to "closed" regions of DNA. (brandeis.edu)
  • 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)
  • Finally, codepletion of Rad51, an important homologous recombination repair protein, abrogates the DNA damage after SET8 depletion. (rupress.org)
  • At the cellular level there are many causes of motor neuron death: DNA mutations, constant oxidative stress, and protein aggregation, among others. (sens.org)
  • The processes that maintain telomeres employ replication protein A (RPA), a single-stranded DNA binding protein. (massgeneral.org)
  • RPA functions as a DNA repair protein that promotes DNA recombination, and the ALT pathway is known to be a process that is dependent on recombination. (massgeneral.org)
  • These phenotypes appear to result, at least in part, from impaired interactions of the mutant β159 clamp protein with the replicative DNA polymerase, Pol III ( 38 ). (asm.org)
  • Since Pol I is a multifunctional protein that participates in DNA replication, as well as numerous DNA repair pathways, several possibilities exist, including Okazaki fragment maturation ( 21 , 31 ) and single-stranded DNA (ssDNA) gap repair ( 16 , 22 ). (asm.org)
  • The RAD51 protein plays essential functions in the HR pathway and is regulated by proteins including the Shu complex (SWSAP1- SWS1-PDS5B-SPIDR), BRCA2, RAD52, and CSB. (nih.gov)
  • A homozygous mutation in the murine resulting in a C\terminal truncation from the protein leads to severe mixed immunodeficiency, SCID 17, and a kinase\inactive DNA\PKcs\mutated protein network marketing leads to Ku70/Ku80\ and p53\reliant embryonic lethality in mice 18. (exposed-skin-care.net)
  • RecA is a widely conserved cytoplasmic protein that performs a range of functions in Escherichia coli, including: DNA repair, homologous recombination, and induction of the SOS pathway. (wisc.edu)
  • Functional annotation clustering showed that they belong to cell cycle, organelle or nuclear lumen, protein transport, and DNA binding and repair clusters. (molvis.org)
  • Each sub-pathway of BER relies on the formation of protein complexes that assemble at the site of the DNA lesion and facilitate repair in a coordinated fashion. (kegg.jp)
  • KIN17, which is known as a DNA and RNA binding protein, is highly expressed in numerous types of human cancers and was discovered to participate in several vital cell behaviors, including DNA replication, damage repair, regulation of cell cycle and RNA processing. (spandidos-publications.com)
  • Previous studies have indicated that KIN17 is involved in global genome repair, DNA replication, transcription and regulation of the cell cycle as part of a multi-protein complex. (spandidos-publications.com)
  • Proliferative control in cancer cells is frequently disrupted by mutations in the retinoblastoma protein (RB) pathway. (bepress.com)
  • RB1 deletion in retinoblastoma protein pathway-disrupted cells results in DNA damage and cancer progression" Molecular and Cellular Biology Vol. 39 Iss. (bepress.com)
  • There is also strong support for a mechanism of action for nasopharyngeal carcinogenesis in which inhaled formaldehyde causes DNA-protein crosslinks in nasopharyngeal tissue. (who.int)
  • 2007) A mutation in EXO1 defines separable roles in DNA mismatch repair and post-replication repair. (yeastgenome.org)
  • In this report, we show EXO1 functions in the MMS2 error-free branch of the PRR pathway independent of the role of EXO1 in DNA mismatch repair (MMR). (yeastgenome.org)
  • Since the Fanconi anemia (FA) pathway coordinates several DNA repair pathways, including homologous recombination in which BRCA1 and BRCA2 play important roles, we investigated whether this pathway harbors other predictors of PARP inhibitor sensitivity. (nih.gov)
  • Cancers that arise as a result of mutation in either BRCA1 or BRCA2 are deficient in specific aspects of DNA repair and are sensitive to drugs that exploit this weakness, unless resistance occurs. (nature.com)
  • As PALB2 exhibits functions in the BRCA1/2-RAD51-dependent homologous DNA recombination repair pathway, we sought to use ex vivo functional screening to explore sensitivity of the tumor cells to therapeutic targeting of DNA repair. (oncotarget.com)
  • BRCA1 hypermethylation confers an HRD, immune cell type, genome-wide DNA methylation, and transcriptional phenotype similar to TNBC tumors with BRCA1-inactivating variants, and it can be observed in matched peripheral blood of patients with tumor hypermethylation. (lu.se)
  • Hypermethylation may be an early event in tumor development that progress along a common pathway with BRCA1-mutated disease, representing a promising DNA-based biomarker for early-stage TNBC. (lu.se)
  • This "in vivo biochemistry" approach has enabled us to demonstrate that there are in fact several independent, competing pathways of homologous recombination, each with its own genetic requirements. (brandeis.edu)
  • Positive selection patterns across Apis reveal a trade-off between maintaining genome stability and generating genetic diversity, with a rapidly evolving piRNA pathway leading to genomes depleted of transposable elements, and a rapidly evolving DNA repair pathway associated with high recombination rates in all Apis species. (nih.gov)
  • Homologous recombination, also known as general recombination, is a type of genetic recombination in which nucleotide sequences are exchanged between two similar or identical strands of DNA. (wikipathways.org)
  • Together these Oncotarget results describe the first ever CAC case with a BRCAness genetic background, evaluate combinatorial DNA repair targeting, and provide a data resource for further analyses of DNA repair targeting in PALB2 deficient cancers. (oncotarget.com)
  • Mutations and/or dysfunction in DDR pathways can lead to unrepaired DNA damage, resulting in genomic instability 4 .Genomic instability, in turn, increases the cell's propensity for genetic alterations that cause cancer initiation and progression 4,5 . (sophiagenetics.com)
  • Advantages of MLST include its precision, allowing simple interlaboratory comparisons, good discrimination between strains, and buffering against the distorting effect of recombination on genetic relatedness. (cdc.gov)
  • Direct and indirect ionization of DNA is ultimately responsible for the DNA alterations that adversely affect the structural and genetic integrity of the system. (cdc.gov)
  • Because of the above, other types of molecular markers may be more useful to infer about failed DNA repair. (nature.com)
  • PARP inhibitors disrupt DNA repair mechanisms by inhibiting PARP enzymatic activity, leading to the accumulation of DNA damage and cell death. (carislifesciences.com)
  • Recombination and fork bypass pathways are the mechanisms accountable for restart of stalled forks. (yeastgenome.org)
  • We discuss what factors determine the sub pathway choice including etiology of the DSB, chromatin structure at the break site, processing of the DSBs and the mechanisms regulating the sub-pathway choice. (springeropen.com)
  • 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)
  • He has discovered novel DNA repair factors linked to human disease, defined the molecular basis through which these factors act, and has uncovered mechanisms by which telomeres protect and maintain chromosomes ends. (royalsociety.org)
  • In the current study, Dr. Heyer and his colleagues used yeast as a model system to elucidate the mechanisms of DNA repair. (bioquicknews.com)
  • JQ1 and ODM-207 were the most potent drugs with known DNA repair targeting mechanisms. (oncotarget.com)
  • The disorders are characterized by a defect in DNA repair mechanisms or genomic stability, and patients with these disorders show increased predisposition to cancer. (medscape.com)
  • In developing lymphocytes, designed DSBs are produced during physiological procedures, such as for example V(D)J recombination and immunoglobulin large chain class change recombination 1, 3. (exposed-skin-care.net)
  • The genome is under constant assault from a multitude of sources that can lead to the formation of DNA double-stand breaks (DSBs). (springeropen.com)
  • 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 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)
  • 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)
  • Cells have evolved with conserved recombination mediated genome editing pathways as a mean for repairing DSBs and restarting replication forks, thus allowing genome duplication to continue [ 8 ]. (springeropen.com)
  • A second NHEJ concomitant pathway often referred to as alternative-NHEJ (Alt-NHEJ), also known as Microhomology-mediated end joining (MMEJ), is another well-studied pathway for repairing DSBs in DNA [ 16 ]. (springeropen.com)
  • Required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ATM-dependent signaling pathways. (thermofisher.com)
  • One of the major DDR pathways is the homologous recombination repair (HRR) pathway, responsible for repairing double-strand breaks (DSBs) in DNA 5 . (sophiagenetics.com)
  • This crosslink can occur within the same strand (intrastrand) or between opposite strands of double-stranded DNA (interstrand). (wikipedia.org)
  • When cisplatin forms interstrand crosslinks (5'-GC), there is a severe distortion to the DNA helix due to a shortened distance between guanines on opposite strands and a cytosine that is flipped out of the helix as a consequence of the GG interaction. (wikipedia.org)
  • The interstrand crosslinks of Mitomycin C are formed in the minor groove of DNA, inducing a moderate widening or stretching to the DNA helix in order to accommodate for the presence of the molecule within the two strands. (wikipedia.org)
  • Telomeres are repetitive noncoding DNA strands at the ends of eukaryotic (plants, animals, etc.) chromosomes. (sens.org)
  • The research team used electron microscopy to observe repair proteins in action on strands of DNA. (bioquicknews.com)
  • Based on the structure of senataxin, researchers believe that it is one of a class of proteins called helicases, which attach to particular regions of DNA or RNA (a chemical cousin of DNA) and temporarily unwind the strands of the molecule. (medlineplus.gov)
  • These fork stalling events have been associated with recombination and gross chromosomal rearrangements. (yeastgenome.org)
  • Inactivation of AP4 in CRC cell lines resulted in increased spontaneous and c-MYC-induced DNA damage, chromosomal instability (CIN) and cellular senescence. (biomedcentral.com)
  • Many characterized crosslinking agents have two independently reactive groups within the same molecule, each of which is able to bind with a nucleotide residue of DNA. (wikipedia.org)
  • Mitomycin C can only act as a crosslinker when a DNA nucleotide has had a reduction to its quinone ring. (wikipedia.org)
  • BER is normally defined as DNA repair initiated by lesion-specific DNA glycosylases and completed by either of the two sub-pathways: short-patch BER where only one nucleotide is replaced and long-patch BER where 2-13 nucleotides are replaced. (kegg.jp)
  • We previously showed that, in somatic cancer cells ectopically producing HSF2BP, DNA damage can trigger HSF2BP-dependent degradation of BRCA2, which prevents HR. Here, we report that, upon binding to BRCA2, HSF2BP forms octameric rings that are able to interlock into a large ring-shaped 24-nucleotide oligomer. (bvsalud.org)
  • Enzymes in base excision (BER), nucleotide excision (NER), double strand break/recombination (DSB/RR), mismatch (MMR), and direct-damage DNA repair pathways are important in the repair of diverse types of DNA damage. (cdc.gov)
  • DNA is composed of alternating sugar and phosphate groups, with the sugar attached to 1 of 4 possible nucleotide bases (adenosine, cytosine, guanine, thymidine). (cdc.gov)
  • BRCA2, along with the recombinase RAD51 , is involved in the repair of DNA double-strand breaks through homologous recombination (HR). Loss of this pathway makes BRCA2-mutant tumours sensitive to DNA cross-linking agents, such as the platinum-based drugs, and also to inhibition of poly (ADP-ribose) polymerase 1 (PARP1), an enzyme involved in DNA repair. (nature.com)
  • RAD51 and/or DMC1 coimmunoprecipitates with REC8, suggesting that REC8 may also provide a basis for assembly of recombination complexes. (rupress.org)
  • We propose that these features drive Rad51 nucleation onto a single position on the DNA to promote formation of uniform pre-synaptic Rad51 filaments in HR. (bvsalud.org)
  • The formation of RAD51/DMC1 filaments on single-stranded (ss)DNAs essential for homology search and strand exchange in DNA double-strand break (DSB) repair is tightly regulated. (bvsalud.org)
  • FIGNL1 AAA+++ ATPase controls RAD51-mediated recombination in human cells. (bvsalud.org)
  • Fignl1 cKO male mice showed defective chromosome synapsis and impaired meiotic DSB repair with the accumulation of RAD51/DMC1 on meiotic chromosomes, supporting a positive role of FIGNL1 in homologous recombination at a post-assembly stage of RAD51/DMC1 filaments. (bvsalud.org)
  • We also showed that purified FIGNL1 dismantles RAD51 filament on double-stranded (ds)DNA as well as ssDNA. (bvsalud.org)
  • We engineered a mouse model with an inducible dominant-negative form of RAD51 (SMRad51) that suppresses RAD51-mediated HR without stimulating alternative mutagenic repair pathways. (bvsalud.org)
  • The remainder maintain telomere length with ALT, a pathway based on homologous recombination (a mechanism used for DNA repair). (sens.org)
  • However, there is evidence that inhibition of telomerase causes cancer cells to switch to the ALT pathway and continue maintaining telomere length. (sens.org)
  • In contrast to the RNA-directed DNA synthesis by telomerase, ALT relies on recombination and replication of telomere DNA to extend telomeres. (massgeneral.org)
  • EXO1 codes for a Rad2p family member nuclease that has been implicated in a multitude of eukaryotic DNA metabolic pathways that include DNA repair, recombination, replication, and telomere integrity. (yeastgenome.org)
  • 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)
  • PARP is a nuclear enzyme essential for single-strand DNA breaks repair. (techscience.com)
  • hybridizationWBwestern blotXLFXRCC4\like factorXRCC4X\ray fix cross\complementing proteins 4 DNA dual\strand break (DSB) may be the most deleterious kind of DNA lesion to a cell, as unrepaired breaks could be lethal to a cell, and wrong fix could cause gross hereditary rearrangements 1, 2, 3. (exposed-skin-care.net)
  • 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)
  • We find that there is a 1000-fold increase in mutation rate and that about half the mutations have a distinctive "signature" suggesting that the DNA polymerase frequently dissociates and re-anneals with its template. (brandeis.edu)
  • Ironically, as both papers point out, it might be the case that the DNA repair defects caused by mutation of BRCA2 increase the likelihood of mutations that lead to the deletion of the 6174delT frameshift and drug resistance. (nature.com)
  • Intriguingly, RB1 mutations can arise late in tumorigenesis in cancer cells whose RB pathway is already compromised by another mutation. (bepress.com)
  • In this study, we present evidence for increased DNA damage and instability in cancer cells with RB pathway defects when RB1 mutations are induced. (bepress.com)
  • DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). (medlineplus.gov)
  • Fogel BL, Perlman S. Novel mutations in the senataxin DNA/RNA helicase domain in ataxia with oculomotor apraxia 2. (medlineplus.gov)
  • Recombination between homologous sequences is a fundamentally important process both in meiosis and in mitotic cells. (brandeis.edu)
  • 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)
  • Cohesion between sister chromatids is essential for proper chromosome disjunction and homologous recombination in the mitotic cycle and in meiosis ( Nasmyth, 2001 ). (rupress.org)
  • Cells with even one mutant copy of RB1 have increased basal levels of DNA damage and increased mitotic errors. (bepress.com)
  • These crosslinking agents only result in small distortions to the DNA helix due to the molecules' smaller size. (wikipedia.org)
  • Homologous recombination involves the precise exchange of similar or identical nucleic acid sequences between two DNA molecules. (cshlpress.com)
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
  • Homologous recombination (HR) is an essential double-stranded DNA break repair pathway. (bvsalud.org)
  • Both homologous recombination, in which the ends of the broken DNA seek out intact templates with the same sequence, and nonhomologous end-joining pathways are found in Saccharomyces as they are in humans. (brandeis.edu)
  • What we discovered is that the DNA repair pathway called recombination is able to reverse itself," said Dr. Wolf-Dietrich Heyer, UC Davis professor of microbiology and of molecular and cellular biology and co-leader of Molecular Oncology at the UC Davis Cancer Center. (bioquicknews.com)
  • DNA crosslinking also has useful merit in chemotherapy and targeting cancerous cells for apoptosis, as well as in understanding how proteins interact with DNA. (wikipedia.org)
  • 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)
  • We have been fascinated by the process of yeast mating-type gene switching, in which cells replace about 700 bp of Ya or Y-specific DNA sequences at the MAT locus by recombining with one of two donor loci, called HMLDescription: image3 and HMRa. (brandeis.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)
  • My project is to develop new high-throughput assays for quantifying activity of the Alternative Lengthening of Telomeres (ALT) pathway in human cells. (sens.org)
  • Cancer cells overcome this replicative senescence in one of two ways: through activating telomerase, an enzyme that extends telomeres, or using another process called the alternative lengthening of telomeres (ALT) pathway. (massgeneral.org)
  • But precisely how the ALT pathway is activated in cancer cells and how it works mechanistically remain largely unclear. (massgeneral.org)
  • And indeed the team found that in cells that use the ALT pathway, RPA binds persistently to telomeres, not detaching after replication. (massgeneral.org)
  • Therefore, the altered capacity of cancer cells to repair and/or replicate DNA is the basis of many classical therapies, such as platinum-based agents, and also recently introduced or upcoming therapies, such as PARP inhibitors or ATR inhibitors (reviewed in refs. (nature.com)
  • It is paramount to identify predictive markers that are associated with failures of DNA maintenance in cancer cells. (nature.com)
  • Abstract Ionizing radiation is frequently used to treat solid tumors, as it causes DNA damage and kill cancer cells. (techscience.com)
  • Inhibiting PARP-1 is lethal in a wide range of cancer cells that lack the homologous recombination repair (HR) pathway. (techscience.com)
  • To help identify the macromolecular target(s) of Cr-dependent oxidative damage, cells deficient for the reduction of phospholipid hydroperoxides ( gpx3 Δ and gpx1 Δ/ gpx2 Δ/ gpx3 Δ) and for the repair of DNA oxidation ( ogg1 Δ and rad30 Δ/ ogg1 Δ) were tested, but were found not to be Cr-sensitive. (microbiologyresearch.org)
  • We discovered that in Bretazenil individual cells, XLF, however, not XRCC4 or PAXX, interacts with DNA\PKcs genetically. (exposed-skin-care.net)
  • To TNFRSF10C elucidate the hereditary connections between DNA\PKcs as well as the XRCC4 paralogues (XRCC4, XLF, PAXX) in individual cells, we utilized knockout individual HAP1 cell lines 23. (exposed-skin-care.net)
  • Simon is Co-founder and VP Science Strategy at Artios Pharma Ltd., a biotech company that is developing DNA repair inhibitors to selectively kill cancer cells. (royalsociety.org)
  • An international team of scientists led by University of California (UC) Davis researchers has discovered that DNA repair in cancer cells is not a one-way street as previously believed. (bioquicknews.com)
  • That makes it a very robust process, allowing cancer cells to deal with DNA damage in many different ways. (bioquicknews.com)
  • This repair mechanism may have something to do with why some cancer cells become resistant to radiation and chemotherapy treatments that work by inducing DNA damage. (bioquicknews.com)
  • Drug screening suggested sensitivity of the PALB2 deficient cells to BET-bromodomain inhibition, and modest sensitivity to DNA-PKi , ATRi, WEE1i and PARPi . (oncotarget.com)
  • To assess DNA repair pathways essential for the tumor cells and contributing to sensitivity/resistance of the tumor cells to BETi, we use ex vivo functional RNAi screening to discover biological insights on the different DNA repair pathways with the PALB2 deficient cells. (oncotarget.com)
  • Figure 4: Analysis of efficacy of targeting different DNA repair pathways on PALB2 mutated CAC cells. (oncotarget.com)
  • Furthermore, Mediator of DNA damage Checkpoint 1 ( MDC1 ), a central component of the DNA damage response and a known target of miR-22-3p, displayed decreased expression in AP4 -deficient cells. (biomedcentral.com)
  • Inhibition of miR-22-3p or ectopic MDC1 expression reversed the increased senescence, DNA damage, CIN and defective HR observed in AP4 -deficient CRC cells. (biomedcentral.com)
  • The DNA in our cells endure up to one million damaging events each day, caused by both exogenous (i.e. environmental) and endogenous (i.e. internal metabolic) factors 3 . (sophiagenetics.com)
  • Although it is unclear how impaired senataxin function leads to the signs and symptoms of ataxia with oculomotor apraxia type 2, some researchers suggest that it disrupts DNA repair and can lead to an accumulation of DNA damage in cells. (medlineplus.gov)
  • A number of direct and indirect radiation interaction pathways can produce damage to the DNA of irradiated cells. (cdc.gov)
  • Cells depend on their DNA for coding information to make various classes of proteins that include enzymes, certain hormones, transport proteins, and structural proteins that support life. (cdc.gov)
  • These crosslinks can, however, be repaired through excision or recombination pathways. (wikipedia.org)
  • An important lesion bypass mechanism is the highly conserved post-replication repair (PRR) pathway that is composed of error-prone translesion and error-free bypass branches. (yeastgenome.org)
  • This is why this pathway if often regarded to be an error-prone recovery mechanism [ 2 , 13 , 14 ]. (springeropen.com)
  • By blocking PARP, the HRD-positive cell can no longer rely on error-prone pathways for DSB repair and the cell dies, a process known as ' synthetic lethality' 5,6 . (sophiagenetics.com)
  • These adducts interfere with cellular metabolism, such as DNA replication and transcription, triggering cell death. (wikipedia.org)
  • Recent studies from our lab and others identified novel additional roles of these proteins in non-canonical repair during DNA lesion recognition, response to replication stress, and transcription coupled repair of replication structures containing R-loops. (nih.gov)
  • They also discuss how these proteins and pathways are strictly regulated to avoid genomic instability, which can lead to diseases such as cancer, and how they are coordinated with other nuclear processes (e.g., transcription and DNA replication). (cshlpress.com)
  • It induces formation of interstrand DNA crosslinks at the amino group of exocyclic N2 of guanine at 5'-CG sequences. (wikipedia.org)
  • Dr. Zou and his team postulated that such cancer cell lines were those without active telomerase, relying instead on the ALT pathway, which lengthens telomeres through recombination with telomeric DNA sequences from the same or other chromosomes. (massgeneral.org)
  • We identified the DNA helicases FANCM and DDX11 as determinants of PARP inhibitor response. (nih.gov)
  • 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)
  • The Escherichia coli dnaN159 allele encodes a mutant form of the β-sliding clamp (β159) that is impaired for interaction with the replicative DNA polymerase (Pol), Pol III. (asm.org)
  • E. coli strains bearing the dnaN159 allele display temperature-sensitive growth ( 14 , 35 , 38 ) and altered DNA polymerase (Pol) usage ( 29 , 38 - 40 ). (asm.org)
  • In contrast to these three Pols, which under certain conditions impede growth of the dnaN159 strain ( 29 , 39 , 40 ), presumably by impairing DNA replication, the catalytic DNA polymerase activity of Pol I ( polA ) is essential for viability of the dnaN159 strain ( 38 ). (asm.org)
  • However, damaged DNA is repaired involving poly-(ADP-ribose) polymerase-1 (PARP-1) causing resistance to radiation therapy. (techscience.com)
  • The reduced ability of β159 to stimulate Pol I in vitro correlates with our finding that single-stranded DNA (ssDNA) gap repair is impaired in the dnaN159 strain. (asm.org)
  • In the SOSS complex, acts as a sensor of single-stranded DNA that binds to single-stranded DNA, in particular to polypyrimidines. (thermofisher.com)
  • Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis. (medlineplus.gov)
  • SET8 depletion causes DNA damage specifically during replication, which induces a Chk1-mediated S-phase checkpoint. (rupress.org)
  • Reaction of chromium(VI) with glutathione or with hydrogen peroxide: identification of reactive intermediates and their role in chromium(VI)-induced DNA damage. (microbiologyresearch.org)
  • Apr 15, 2003 - Dr. Qingyi Wei, M.D. Anderson, Houston, Tx - DNA Repair Function, Polymorphisms and Cancer Risk in the General Population Mar 11, 2003 - Dr. Sankar Mitra, Univ of Texas, Galveston - Oxidative Damage Repair and Its Co-ordination in the Mammalian Genome. (bio.net)
  • March 05, 2003 - Dr. Stephen J. Elledge - Baylor College of Medicine Houston, TX - Sensing and Responding to DNA Damage [Note: this talk was part of the NIH Wed afternoon lecture series and was sponsored by: the Mouse Club and Washington Area Yeast Club Interest Group and is now posted on the DNA Repair Interest Group part of the videocast.nih.gov website. (bio.net)
  • Nov 12, 2002 - Dr. Rob Sobol, Univ of Pittsburgh - DNA Base Damage and Repair Intermediates: Out of the Pan and into the Fire [Note: The posting of this talk will be delayed at the request of the speaker. (bio.net)
  • PARP plays a key role in the process of DNA damage repair. (frontiersin.org)
  • This review provides an overview of DNA damage and repair pathways, with a focus on HRD, and discusses major advances in targeting these pathways in skin cancers. (carislifesciences.com)
  • In summary, AP4, miR-22-3p and MDC1 form a conserved and coherent, regulatory feed-forward loop to promote DNA repair, which suppresses DNA damage, senescence and CIN, and contributes to 5-FU resistance. (biomedcentral.com)
  • Addition of BRME1 leads to dissociation of both of these ring structures and cancels the disruptive effect of HSF2BP on cancer cell resistance to DNA damage. (bvsalud.org)
  • Elevated levels of reactive oxygen species as well as impaired homologous recombination repair underlie this DNA damage. (bepress.com)
  • These events activate a complex network of DNA damage response (DDR) pathways , which facilitate DNA repair and maintain the stability of the genome 4 . (sophiagenetics.com)
  • Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing. (medlineplus.gov)
  • DNA damage occurs by indirect action (mediated through radiolytic products in water) or direct ionization. (cdc.gov)
  • Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers all aspects of recombinational DNA repair, meiotic recombination, and the regulation of these processes. (cshlpress.com)
  • Simon's work has helped shape our understanding of the regulation and execution of homologous recombination, a key DNA repair pathway frequently inactivated in cancer. (royalsociety.org)
  • Furthermore, KIN17 is associated with cancer cell proliferation, migration, invasion and cell cycle regulation by regulating pathways including the p38 MAPK, NF‑κB‑Snail and TGF‑β/Smad2 signaling pathways. (spandidos-publications.com)
  • This volume is an indispensable reference for biochemists, molecular biologists, and cell biologists who want to understand how DNA recombination maintains genomic integrity in individual organisms and across generations. (cshlpress.com)
  • This process of complex formation appears to provide an increase in specificity and efficiency to the BER pathway, thereby facilitating the maintenance of genome integrity by preventing the accumulation of highly toxic repair intermediates. (kegg.jp)
  • Homologous recombination (HR) is a prominent DNA repair pathway maintaining genome integrity. (bvsalud.org)
  • SUMO-Chain-Regulated Proteasomal Degradation Timing Exemplified in DNA Replication Initiation. (ifom.eu)
  • Rag-1 and Rag-2 and initiation of Ig recombination events [7]. (lu.se)
  • Prevention of unwanted recombination at damaged replication forks. (ifom.eu)
  • The Mgs1/WRNIP1 ATPase is required to prevent a recombination salvage pathway at damaged replication forks. (ifom.eu)
  • 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)
  • Endogenous crosslinking agents are compounds and metabolites that are introduced from cellular or biochemical pathways within a cell or organism. (wikipedia.org)
  • if immediate recombination does not occur, these can manifest as some type of molecular, cellular, or organic system alteration. (cdc.gov)
  • Their findings show instead that recombination, an important DNA repair process, has a self-correcting mechanism that allows DNA to make a virtual u-turn and start over. (bioquicknews.com)
  • The telomerase pathway is well-studied and inhibitors are in clinical trials. (sens.org)
  • 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)
  • Oncotarget published " Ex vivo analysis of DNA repair targeting in extreme rare cutaneous apocrine sweat gland carcinoma " which reported a rare metastatic case with a PALB2 aberration identified previously as a familial susceptibility gene for breast cancer in the Finnish population. (oncotarget.com)
  • It also prevents BRCA2 degradation during interstrand DNA crosslink repair in Xenopus egg extracts. (bvsalud.org)
  • New research from Mass General Cancer Center provides a detailed map of the less-common ALT pathway that could inform novel treatments. (massgeneral.org)
  • Can the ALT pathway be disrupted to treat cancer? (massgeneral.org)
  • Because cancer therapeutics often target DNA synthesis or repair, we asked if mutational signatures make useful markers of drug sensitivity. (nature.com)
  • Many commonly employed cancer drugs act by interfering with DNA synthesis or maintenance or by damaging DNA. (nature.com)
  • Because mutational signatures describe the state of the DNA repair machinery of a cancer cell, they may be able to serve as a drug sensitivity marker. (nature.com)
  • Jan 21, 2003 - Tues 12:30PM - Dr. Jack Taylor, NIEHS - Epidemiologic studies of DNA repair gene polymorphisms and cancer risk Dec 17, 2002 - Dr. John Tainer, UC Berkeley - Conformational Controls and DNA Repair Coordination - [Note: The posting of this talk will be delayed at the request of the speaker. (bio.net)
  • DNA was obtained from 451 controls with no self-reported cancer and from 316 cases. (cdc.gov)
  • The primary factors contain Ku70, Ku80, X\ray fix cross\complementing proteins 4 (XRCC4), and DNA ligase IV (LIG4), as the accessories factors consist of XRCC4\like aspect (XLF), DNA\reliant proteins kinase catalytic subunit (DNA\PKcs), paralogue of XRCC4 and XLF (PAXX), and modulator of retroviral an infection (MRI). (exposed-skin-care.net)
  • For instance, DNA\PKcs is normally a serine/threonine kinase, a known person in the phosphatidylinositol\3\kinase\like kinase family members, which also contains ataxia\telangiectasia mutated (ATM) proteins kinase 16. (exposed-skin-care.net)
  • However, this process seems to be related to pathways other than transcriptional control. (nih.gov)