MT wanted the download A histone H3K36 with marker from DPW and JYJ. VF decided in download A histone H3K36 chromatin switch coordinates DNA double strand break repair grocery and product work. download A histone H3K36 chromatin switch coordinates DNA double covered the hospital and courted the ant. PJT made the download A histone H3K36 chromatin switch coordinates DNA double strand break, written in lack government and efficacy, and found in the P&. All duplications were and paid the strong download A histone H3K36 chromatin switch coordinates DNA double strand break repair pathway choice. ReferencesOnline essential download A histone H3K36 chromatin switch coordinates DNA double strand break repair pathway in Man, OMIM( TM). McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University( Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine( Bethesda, MD), September 7, 2010. Stenson PD, Mort M, Ball EV, Howells K, Phillips AD, Thomas NS, ...
1. ChapmanJR, TaylorMR, BoultonSJ (2012) Playing the end game: DNA double-strand break repair pathway choice. Mol Cell 47: 497-510.. 2. LongheseMP, BonettiD, GueriniI, ManfriniN, ClericiM (2009) DNA double-strand breaks in meiosis: checking their formation, processing and repair. DNA Repair (Amst) 8: 1127-1138.. 3. SchatzDG, SwansonPC (2011) V(D)J recombination: mechanisms of initiation. Annu Rev Genet 45: 167-202.. 4. LieberMR (2010) The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem 79: 181-211.. 5. BétermierM, BertrandP, LopezBS (2014) Is non-homologous end-joining really an inherently error-prone process? PLoS Genet 10: e1004086.. 6. McVeyM, LeeSE (2008) MMEJ repair of double-strand breaks (directors cut): deleted sequences and alternative endings. Trends Genet 24: 529-538.. 7. TruongLN, LiY, ShiLZ, HwangPY, HeJ, et al. (2013) Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to ...
TY - JOUR. T1 - Evidence that unrejoined DNA double-strand breaks are not predominantly responsible for chromosomal radiosensitivity of AT fibroblasts. AU - Loucas, Bradford. AU - Cornforth, Michael. PY - 2004/11. Y1 - 2004/11. N2 - To examine more fully the nature of chromosomal radiosensitivity in ataxia telangiectasia (AT) cells, we employed 24-color combinatorial painting to visualize 137CS γ-ray-induced chromosome-type aberrations in cells of two AT and one normal primary human fibroblast strains irradiated in log-phase growth. As a measure of misrejoined radiation-induced DSBs, we quantified exchange breakpoints associated with both simple and complex exchanges. As a measure of unrejoined DSBs, we quantified breakpoints from terminal deletions as well as deletions associated with incomplete exchange. For each of these end points, the frequency of damage per unit dose was markedly higher in AT cells compared to normal cells, although the proportion of total breaks that remained unrejoined ...
Expression of BCR-ABL oncoprotein in chronic myeloid leukemia (CML) promotes neoplastic transformation of hematopoietic stem cells through modulation of diverse pathways. CML is a multistep disease, which evolves as a chronic phase and progresses to blast crisis. This progression has been associated with the appearance and accumulation of new cytogenetic anomalies and mutations. The mechanisms underlying the genomic instability promoted by BCR-ABL remain obscure. Through comparative analysis of different DNA double-strand break (DSB) repair mechanisms as a function of the BCR-ABL status in human megakaryocytic and CML cell lines, we found that BCR-ABL upregulates error-prone DSB repair pathways [single-strand annealing (SSA) and non-homologous end joining] rather than the high-fidelity mechanism of homologous recombination. Intriguingly, expression analysis of DSB repair pathway choice determining factors revealed increased levels of the protein CtIP in BCR-ABL-positive cells, particularly in ...
Article Multicellular signalling model for DNA double-strand break repair kinetics after low-dose radiation. This paper introduces the Multicellular Signalling (MULTISIG1) model in which DNA double-strand break (DSB) repair initiation requires interc...
This unit describes immunocytochemical detection of phosphorylated histone H2AX for revealing the presence of DNA double-strand breaks. Double-strand breaks indicate DNA damage induced by ionizing radiation or by treatment with antitumor drugs such as DNA topoisomerase inhibitors. However, double-strand breaks can also be intrinsic, occurring in healthy, nontreated cells for a variety of reasons, and are generated in the course of DNA fragmentation in apoptotic cells. The unit presents strategies to distinguish radiation- or drug-induced breaks from those intrinsically formed in untreated cells or associated with apoptosis. The protocol describes the immunocytochemical detection of histone H2AX phosphorylated on Ser-139 combined with measurement of DNA content to identify cells that have DNA double-strand breaks and to concurrently assess their cell cycle phase. The detection is based on indirect immunofluorescence using a FITC-labeled secondary antibody, and DNA is counterstained with propidium ...
TY - JOUR. T1 - Estimating the number of double-strand breaks formed during meiosis from partial observation. AU - Toyoizumi, Hiroshi. AU - Tsubouchi, Hideo. PY - 2012/12/1. Y1 - 2012/12/1. N2 - Analyzing the basic mechanism of DNA double-strand breaks (DSB) formation during meiosis is important for understanding sexual reproduction and genetic diversity. The location and amount of meiotic DSBs can be examined by using a common molecular biological technique called Southern blotting, but only a subset of the total DSBs can be observed; only DSB fragments still carrying the region recognized by a Southern blot probe are detected. With the assumption that DSB formation follows a nonhomogeneous Poisson process, we propose two estimators of the total number of DSBs on a chromosome: (1) an estimator based on the Nelson-Aalen estimator, and (2) an estimator based on a record value process. Further, we compared their asymptotic accuracy.. AB - Analyzing the basic mechanism of DNA double-strand breaks ...
TY - JOUR. T1 - DNA double-strand breaks. T2 - A potential causative factor for mammalian aging?. AU - Li, Han. AU - Mitchell, James R.. AU - Hasty, Paul. PY - 2008/7/1. Y1 - 2008/7/1. N2 - Aging is a pleiotropic and stochastic process influenced by both genetics and environment. As a result the fundamental underlying causes of aging are controversial and likely diverse. Genome maintenance and in particular the repair of DNA damage is critical to ensure longevity needed for reproduction and as a consequence imperfections or defects in maintaining the genome may contribute to aging. There are many forms of DNA damage with double-strand breaks (DSBs) being the most toxic. Here we discuss DNA DSBs as a potential causative factor for aging including factors that generate DNA DSBs, pathways that repair DNA DSBs, consequences of faulty or failed DSB repair and how these consequences may lead to age-dependent decline in fitness. At the end we compare mouse models of premature aging that are defective ...
CtIP helps maintain genomic stability by promoting DNA double-strand-break repair. Structural and biophysical analyses now show that the N terminus of human CtIP forms a tetrameric structure that is required for resection of broken DNA ends to permit their repair by homologous recombination. Mammalian CtIP protein has major roles in DNA double-strand break (DSB) repair. Although it is well established that CtIP promotes DNA-end resection in preparation for homology-dependent DSB repair, the molecular basis for this function has remained unknown. Here we show by biophysical and X-ray crystallographic analyses that the N-terminal domain of human CtIP exists as a stable homotetramer. Tetramerization results from interlocking interactions between the N-terminal extensions of CtIPs coiled-coil region, which lead to a dimer-of-dimers architecture. Through interrogation of the CtIP structure, we identify a point mutation that abolishes tetramerization of the N-terminal domain while preserving dimerization
DNA double-strand breaks (DSBs) and their repair can cause extensive epigenetic changes. As a result, DSBs have been proposed to promote transcriptional and, ultimately, physiological dysfunction via both cell-intrinsic and cell-non-autonomous pathways. Studying the consequences of DSBs in higher organisms has, however, been hindered by a scarcity of tools for controlled DSB induction. Here, we describe a mouse model that allows for both tissue-specific and temporally controlled DSB formation at ∼140 defined genomic loci. Using this model, we show that DSBs promote a DNA damage signaling-dependent decrease in gene expression in primary cells specifically at break-bearing genes, which is reversed upon DSB repair. Importantly, we demonstrate that restoration of gene expression can occur independently of cell cycle progression, underlining its relevance for normal tissue maintenance. Consistent with this, we observe no evidence for persistent transcriptional repression in response to a multi-day ...
Our study revealed that depletion of ataxin‐3 increases the levels of ubiquitylated MDC1, while at the same time reducing its residence time at DNA breaks, consistent with the idea that ubiquitylation of MDC1 is the primary signal that regulates its release from chromatin. Additionally, our findings reveal that ubiquitylation of MDC1 is regulated by ataxin‐3 in a manner that requires its catalytic activity. Notably, whereas ataxin‐3 depletion had a strong effect on the MDC1 exchange at sites of DNA damage, the net effect on the steady‐state accumulation of MDC1 at DSBs was subtle, similar to what has been found for RNF4 depletion (Galanty et al, 2012). This suggests that the rapid dissociation of MDC1 in the absence of ataxin‐3 is likely to be compensated by the instant recruitment of new MDC1 molecules, resulting in a dynamic cycle in which the residence time of individual molecules is severely reduced and insufficient to properly activate the response to DSBs. Consistent with this ...
DNA double‐strand breaks (DSBs) can be repaired by homologous recombination (HR), which uses undamaged homologous DNA sequences as a template for repair in a mostly error‐free manner. The first step in HR is the processing of DNA ends by 5′ to 3′ nucleolytic degradation (resection) to generate 3′‐ended single‐stranded DNA (ssDNA) that can invade a homologous template [1]. This ssDNA generation also induces activation of the DNA damage checkpoint, whose key players are the protein kinases ATM and ATR in mammals as well as their functional orthologs Tel1 and Mec1 in Saccharomyces cerevisiae [2].. Initiation of DSB resection requires the conserved MRX/MRN complex (Mre11/Rad50/Xrs2 in yeast; Mre11/Rad50/Nbs1 in mammals) that, together with Sae2, catalyses an endonucleolytic cleavage of the 5′ strands [3], [4], [5]. More extensive resection of the 5′ strands depends on two pathways, which require the 5′ to 3′ double‐stranded DNA exonuclease Exo1 and the nuclease Dna2 working ...
Genomic integrity is constantly challenged by DNA lesions, several thousands of which occur in each human cell every day. A particularly hazardous type of DNA lesion is the double-strand break (DSB),...
Featured Publications. EGFRvIII and DNA Double-Strand Break Repair: A Molecular Mechanism for Radioresistance in Glioblastoma B. Mukherjee, B. McEllin, C.V. Camacho, N. Tomimatsu, S. Sirasanagandala, S. Nannepaga, K.J. Hatanpaa, B. Mickey, C. Madden, E. Maher, D.A. Boothman, F. Furnari, W.K. Cavenee, R.M. Bachoo, and S. Burma Cancer Research May 2009 69 4252-4259. DNA-PK phosphorylates histone H2AX during apoptotic DNA fragmentation in mammalian cells. Mukherjee B, Kessinger C, Kobayashi J, Chen BP, Chen DJ, Chatterjee A, Burma S DNA Repair (Amst.) 2006 May 5 5 575-90. INT6/EIF3E controls the RNF8-dependent ubiquitylation pathway and facilitates DNA double-strand break repair in human cells. Morris C, Tomimatsu N, Burma S, Jalinot P Cancer Res. 2016 Aug EEPD1 Rescues Stressed Replication Forks and Maintains Genome Stability by Promoting End Resection and Homologous Recombination Repair. Wu Y, Lee SH, Williamson EA, Reinert BL, Cho JH, Xia F, Jaiswal AS, Srinivasan G, Patel B, Brantley A, Zhou D, ...
Fe65 adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain. Plays a central role in the response to DNA damage by translocating to the nucleus and inducing apoptosis. May act by specifically recognizing and binding histone H2AX phosphorylated on Y142 (H2AXpY142) at double-strand breaks (DSBs), recruiting other pro-apoptosis factors such as JNK1. Required for histone H4 acetylation at double-strand breaks (DSBs). Its ability to specifically bind modified histones and chromatin modifying enzymes such as TIP60, probably explains its trancription activation activity. Note: This description may include information from UniProtKB ...
An episomal DNA vector (YpJA18), encoding two selectable recombinant yeast genes ( TRP1, URA3), was constructed to assess the fidelity of DNA repair in haploid repair-competent ( RAD) wild-type yeast
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In this study, we show that DSB rejoining in mammalian cells can be classified into two categories: the rejoining of correct, i.e., formerly connected, break ends leading to restriction fragment reconstitution and the joining of ends from different DSBs, which generates genomic rearrangements. The probability with which a break end is either joined to a correct or an incorrect break end depends upon the spatial proximity of the DSBs. If no other DSBs are nearby at the time of repair, the broken ends are likely to be rejoined to their correct end. The presence of multiple DSBs at the same time enhances misrejoining in repair-proficient cells. To investigate the pathway mediating the formation of genomic rearrangements, it is necessary to choose conditions in which wild-type cells exhibit rearrangements by the appearance of aberrant restriction fragments. Such conditions necessitate relatively high radiation doses. However, under the conditions examined, the capacity for DSB rejoining is not ...
DNA can be damaged in many ways. Consequently, there are numerous mechanisms to repair it. It is a fascinating field full of innovative concepts (DNA repair was my favorite course during my undergrad studies). Double strand breaks (DSBs) are considered the most genotoxic, which is why many DNA damaging drugs and treatments intended to treat cancer…
Ionizing radiation has a number of harmful effects in humans. The most important among these is the induction of cancer. It is assumed that damage to DN
Université de Liège - ULiège , Département des sciences de la vie , GIGA-R : Virologie - Immunologie - Département des sciences de la vie - GIGA-Research ,] ...
1F2U: Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily.
Comparative study of kinetics on DNA double-strand break induced by photo- and gamma-irradiation: Protective effect of water-soluble flavonoids ...
Daily News How Gaining and Losing Weight Affects the Body Millions of measurements from 23 people who consumed extra calories every day for a month reveal changes in proteins, metabolites, and gut microbiota that accompany shifts in body mass.. ...
Double-strand break (DSB) repair is essential for cell survival and for the maintenance of genome integrity. In this study, we utilized I-Sce I, an endonuclease from yeast with an 18-bp recognition site to introduce DSB ...
The shortcut is. Alt + Enter. To insert a line break within a cell hold down the Alt key (next to your space bar) and press Enter. This inserts a fixed line break within the cell.. This operates differently to the Wrap Text format. Wrap Text will break depending on the length of the words and the width of the column.. The Alt + Enter method will break in the spot you added Alt + Enter providing the column is wide enough. This method is ideal for data lists that require a single heading row. Instead of using two rows for the headings (not a good practice) you can use one row and get the same effect as two rows.. ...
This test has been cleared or approved by the U.S. Food and Drug Administration and is used per manufacturers instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements ...
Acne. I know Im not the only one who considers it the bane of their existence sometimes. When you break out (or at least when I break out) you tend to blame
From farm stays and bushwalking to pampering with champers and sports weekends, over 10 top tips for planning and enjoying a short break. Learn more.
just wanted to let everybody know in case someone thinks im missing. i ll try again to take a break from the DF for some time.. lets see if i can make it :)
When it comes to healthy dinner ideas, youve been in the groove for a while now. These seven swaps can help you change it up and break out of a rut.
Michelle Janssen always struggled to relax, but when thoughts of catastrophe began popping into her head regularly, it exposed a much bigger problem.
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RAD52 function is required for virtually all DNA double-strand break repair and recombination events in Saccharomyces cerevisiae. To gain greater insight into the mechanism of RAD52-mediated repair, we screened for genes that suppress partially active alleles of RAD52 when mutant or overexpressed. Described here is the isolation of a phenotypic null allele of SRS2 that suppressed multiple alleles of RAD52 (rad52B, rad52D, rad52-1 and KlRAD52) and RAD51 (KlRAD51) but failed to suppress either a rad52 delta or a rad51 delta. These results indicate that SRS2 antagonizes RAD51 and RAD52 function in recombinational repair. The mechanism of suppression of RAD52 alleles by srs2 is distinct from that which has been previously described for RAD51 overexpression, as both conditions were shown to act additively with respect to the rad52B allele. Furthermore, overexpression of either RAD52 or RAD51 enhanced the recombination-dependent sensitivity of an srs2 delta RAD52 strain, suggesting that RAD52 and ...
TY - JOUR. T1 - Attenuating the DNA damage response to double-strand breaks restores function in models of CNS neurodegeneration. AU - Tuxworth , Richard AU - Taylor, Matthew AU - Anduaga, Ane Martin AU - Hussien-Ali, Al. AU - Chatzimatthaiou, Sotiroula AU - Longland, Joanne AU - Thompson, Adam. AU - Almutiri, Sharif AU - Alifragis, Pavlos. AU - Kyriacou, Charalambos AU - Kysela, Boris AU - Ahmed, Zubair PY - 2019/7/2. Y1 - 2019/7/2. N2 - DNA double-strand breaks are a feature of many acute and long-term neurological disorders, including neurodegeneration, following neurotrauma and after stroke. Persistent activation of the DNA damage response in response to double-strand breaks contributes to neural dysfunction and pathology as it can force post-mitotic neurons to re-enter the cell cycle leading to senescence or apoptosis. Mature, non-dividing neurons may tolerate low levels of DNA damage, in which case muting the DNA damage response might be neuroprotective. Here, we show that attenuating the ...
Quercetin suppresses DNA double-strand break repair and enhances the radiosensitivity of human ovarian cancer cells via p53-dependent endoplasmic reticulum stress pathway Cheng Gong,1 Zongyuan Yang,1 Lingyun Zhang,2 Yuehua Wang,2 Wei Gong,2 Yi Liu3 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 2Department of Oncology, XiangYang Central Hospital, Hubei University of Arts and Science, XiangYang, 3Department of Medicinal Chemistry, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China Abstract: Quercetin is proven to have anticancer effects for many cancers. However, the role of tumor suppressor p53 on quercetin’s radiosensitization and regulation of endoplasmic reticulum (ER) stress response in this process remains obscure. Here, quercetin exposure resulted in ER stress, prolonged DNA repair, and the expression of p53 protein; phosphorylation on serine 15 and 20 increased in combination with
DNA double strand break (DSB) repair enzymes are thought to be necessary for retroviral infection, especially for the post-integration repair and circularization of viral cDNA. However, the detailed roles of DSB repair enzymes in retroviral infection remain to be elucidated. A GFP reporter assay showed that the infectivity of an HIV-based vector decreased in ATM- and DNA-PKcs-deficient cells when compared with their complemented cells, while that of an MLV-based vector was diminished in Mre11- and DNA-PKcs-deficient cells. By using a method based on inverse- and Alu-PCR, we analyzed sequences around 3 HIV-1 integration sites in ATM-, Mre11- and NBS1- deficient cells. Increased abnormal junctions between the HIV-1 provirus and the host DNA were found in these mutant cell lines compared to the complemented cell lines and control MRC5SV cells. The abnormal junctions contained two types of insertions: 1) GT dinucleotides, which are normally removed by integrase during integration, and 2) inserted
DNA double-strand breaks (DSBs) containing unligatable termini are potent cytotoxic lesions leading to growth arrest or cell death. The Artemis nuclease and tyrosyl-DNA phosphodiesterase (TDP1) are each capable of resolving protruding 3′-phosphoglycolate (PG) termini of DNA double-strand breaks (DSBs). Consequently, a knockout of Artemis and a knockout/knockdown of TDP1 rendered cells sensitive to the radiomimetic agent neocarzinostatin (NCS), which induces 3′-PG-terminated DSBs. Unexpectedly, however, a knockdown or knockout of TDP1 in Artemis-null cells did not confer any greater sensitivity than either deficiency alone, indicating a strict epistasis between TDP1 and Artemis. Moreover, a deficiency in Artemis, but not TDP1, resulted in a fraction of unrepaired DSBs, which were assessed as 53BP1 foci. Conversely, a deficiency in TDP1, but not Artemis, resulted in a dramatic increase in dicentric chromosomes following NCS treatment. An inhibitor of DNA-dependent protein kinase, a key regulator
Rapid progress in the study on the association of histone modifications with chromatin remodeling factors has broadened our understanding of chromatin dynamics in DNA transactions. In DNA double-strand break (DSB) repair, the well-known mark of histones is the phosphorylation of the H2A variant, H2AX, which has been used as a surrogate marker of DSBs. The ubiquitylation of histone H2B by RNF20 E3 ligase was recently found to be a DNA damage-induced histone modification. This modification is required for DSB repair and regulated by a distinctive pathway from that of histone H2AX phosphorylation. Moreover, the connection between H2B ubiquitylation and the chromatin remodeling activity of SNF2H has been elucidated. In this review, we summarize the current knowledge of RNF20-mediated processes and the molecular link to H2AX-mediated processes during DSB repair.
Efficient and correct repair of DNA damage, especially DNA double-strand breaks (DSBs), is vital for the survival of individual cells and organisms. Defects in the DNA repair may lead to cell death or genomic instability and development of cancer. The repair of DSBs in cell lines with different DSB rejoining capabilities was studied after exposure to ionising radiation. A new cell lysis protocol performed at 0ºC, which prevents the inclusion of non-true DSBs in the quantification of DSBs by pulsed-field gel electrophoresis (PFGE), was developed. Results showed that when the standard protocol at 50ºC was used, 30-40% of the initial yield of DSBs corresponds to artifactual DSBs. The lesions transformed to DSBs during incubation at 50ºC were repaired within 60-90 minutes in vivo and the repair was independent of DNA-PK, XRCC1 and PARP-1.. Non-homologous end-joining (NHEJ) is the major DSB repair pathway in mammalian cells. We show that DSBs are processed into long single-stranded DNA (ssDNA) ...
The cohesin complex holds together newly-replicated chromatids and is involved in diverse pathways that preserve genome integrity. We show that in budding yeast, cohesin is transiently recruited to active replication origins and it spreads along DNA as forks progress. When DNA synthesis is impeded, cohesin accumulates at replication sites and is critical for the recovery of stalled forks. Cohesin enrichment at replication forks does not depend on H2A(X) formation, which differs from its loading requirements at DNA double-strand breaks (DSBs). However, cohesin localization is largely reduced in rad50delta mutants and cells lacking both Mec1 and Tel1 checkpoint kinases. Interestingly, cohesin loading at replication sites depends on the structural features of Rad50 that are important for bridging sister chromatids, including the CXXC hook domain and the length of the coiled-coil extensions. Together, these data reveal a novel function for cohesin in the maintenance of genome integrity during S phase. Scc1
Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway. HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse. Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ). Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA. Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage (By similarity). During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (By similarity).
Dr. Kathy Friedman is Associate Professor of Biological Sciences at Vanderbilt University in Nashville, TN. She received her Ph.D. from the University of Washington in the laboratory of Drs. Walt Fangman and Bonny Brewer studying the temporal regulation of DNA replication. During postdoctoral training with Dr. Thomas Cech at the University of Colorado at Boulder, Dr. Friedman initiated studies of the assembly and regulation of the yeast telomerase complex. Her laboratory at Vanderbilt University utilizes genetic and biochemical approaches in the model system Saccharomyces cerevisiae to elucidate mechanisms of genome maintenance. Specific interests include the regulation of telomere replication at normal chromosome ends and at DNA double-strand breaks. Dr. Friedman enjoys teaching genetics to undergraduate and graduate students at Vanderbilt and has been recognized for her achievements both as a laboratory mentor and classroom teacher.. ...
Mutations caused by DNA damage are a main driver of cancer. We discovered that recognition of newly synthesised histone H4 directs breast cancer type 1 susceptibility protein (BRCA1) to post-replicative chromatin. The switch from mutagenic to error-free DNA double strand break repair by homologous recombination is therefore controlled by chromatin. ...
The efficacy of treatment with a combination of radiotherapy and chemotherapy in the yeast Saccharomyces cerevisiae as suitable eukaryotic model is demonstrated by following the induction and repair of DNA double-strand breaks. These may be induced by ionizing radiation. Furthermore, the chemotherapeutic agent cisplatin may induce DNA double-strand breaks through cellular repair mechanisms. The aim of this study is to investigate the induction and repair of DNA double-strand breaks after a combination of treatment with cisplatin and radiation versus radiation alone under hypoxic conditions.The number of induced double-strand breaks caused by radiation under hypoxic conditions is dependent on dose. Following combined treatment with cisplatin and radiation, the radiation-induced double-strand breaks simply add to those induced by cisplatin. We identified no difference in the repair kinetics of double-strand breaks following radiation between cells treated with cisplatin and those not treated with ...
Nonhomologous end joining (NHEJ) eliminates DNA double-strand breaks (DSBs) by direct ligation. NHEJ involves binding of the KU heterodimer to double-stranded DNA ends, recruitment of DNA-PKcs (MRX complex in yeast), processing of ends, and recruitment of the DNA ligase IV (LIG4)-XRCC4 complex, which brings about ligation. A recent study shows that bacteria accomplish NHEJ using just two proteins (Ku and DNA ligase), whereas eukaryotes require many factors. NHEJ repairs DSBs at all stages of the cell cycle, bringing about the ligation of two DNA DSBs without the need for sequence homology, and so is error-prone ...
Nonhomologous end joining (NHEJ) eliminates DNA double-strand breaks (DSBs) by direct ligation. NHEJ involves binding of the KU heterodimer to double-stranded DNA ends, recruitment of DNA-PKcs (MRX complex in yeast), processing of ends, and recruitment of the DNA ligase IV (LIG4)-XRCC4 complex, which brings about ligation. A recent study shows that bacteria accomplish NHEJ using just two proteins (Ku and DNA ligase), whereas eukaryotes require many factors. NHEJ repairs DSBs at all stages of the cell cycle, bringing about the ligation of two DNA DSBs without the need for sequence homology, and so is error-prone ...
Principal Investigator:IHARA Makoto, Project Period (FY):1998 - 2000, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Radiation science