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https://www.readbyqxmd.com/read/28089177/cell-cycle-dependent-positive-and-negative-functions-of-fun30-chromatin-remodeler-in-dna-damage-response
#1
Jasmine Siler, Bowen Xia, Carina Wong, Morgan Kath, Xin Bi
The evolutionally conserved Fun30 chromatin remodeler in Saccharomyces cerevisiae has been shown to contribute to cellular resistance to genotoxic stress inflicted by camptothecin (CPT), methyl methanesulfonate (MMS) and hydroxyurea (HU). Fun30 aids in extensive DNA resection of DNA double stranded break (DSB) ends, which is thought to underlie its role in CPT-resistance. How Fun30 promotes MMS- or HU-resistance has not been resolved. Interestingly, we have recently found Fun30 to also play a negative role in cellular tolerance to MMS and HU in the absence of the Rad5-dependent DNA damage tolerance pathway...
January 5, 2017: DNA Repair
https://www.readbyqxmd.com/read/28077781/effects-of-an-unusual-poison-identify-a-lifespan-role-for-topoisomerase-2-in-saccharomyces-cerevisiae
#2
Gregory Tombline, Jonathan I Millen, Bogdan Polevoda, Matan Rapaport, Bonnie Baxter, Michael Van Meter, Matthew Gilbertson, Joe Madrey, Gary A Piazza, Lynn Rasmussen, Krister Wennerberg, E Lucile White, John L Nitiss, David S Goldfarb
A progressive loss of genome maintenance has been implicated as both a cause and consequence of aging. Here we present evidence supporting the hypothesis that an age-associated decay in genome maintenance promotes aging in Saccharomyces cerevisiae (yeast) due to an inability to sense or repair DNA damage by topoisomerase 2 (yTop2). We describe the characterization of LS1, identified in a high throughput screen for small molecules that shorten the replicative lifespan of yeast. LS1 accelerates aging without affecting proliferative growth or viability...
January 5, 2017: Aging
https://www.readbyqxmd.com/read/28075014/knockdown-of-rev3-synergizes-with-atr-inhibition-to-promote-apoptosis-induced-by-cisplatin-in-lung-cancer-cells
#3
He-Guo Jiang, Ping Chen, Jin-Yu Su, Ming Wu, Hai Qian, Yi Wang, Jian Li
It has been demonstrated that REV3, the catalytic subunit of the translesion synthesis (TLS) polymerase ζ, play an important role in DNA damage response (DDR) induced by cisplatin, and Ataxia telangietasia mutated and Rad-3-related (ATR) knase is a central player in activating cell cycle checkpoint, stabilizing replication forks, regulating DDR, and promoting repair of DNA damage caused by cisplatin. Cancer cells deficient in either one of REV3 and ATR are more sensitive to cisplatin. However, whether co-inhibition of REV3 and ATR can further increase sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin is not clear...
January 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28065599/homology-requirements-and-competition-between-gene-conversion-and-break-induced-replication-during-double-strand-break-repair
#4
Anuja Mehta, Annette Beach, James E Haber
Saccharomyces cerevisiae mating-type switching is initiated by a double-strand break (DSB) at MATa, leaving one cut end perfectly homologous to the HMLα donor, while the second end must be processed to remove a non-homologous tail before completing repair by gene conversion (GC). When homology at the matched end is ≤150 bp, efficient repair depends on the recombination enhancer, which tethers HMLα near the DSB. Thus, homology shorter than an apparent minimum efficient processing segment can be rescued by tethering the donor near the break...
December 22, 2016: Molecular Cell
https://www.readbyqxmd.com/read/28054567/break-induced-replication-an-unhealthy-choice-for-stress-relief
#5
Juraj Kramara, Beth Osia, Anna Malkova
No abstract text is available yet for this article.
January 5, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28052067/the-paradoxical-effects-of-different-hepatitis-c-viral-loads-on-host-dna-damage-and-repair-abilities
#6
Shu-Chi Wang, Kuan-Ru Lai, Chia-Yang Li, Chi-Shiun Chiang, Guann-Yi Yu, Naoya Sakamoto, Wen-Yu Tu, Meng-Hsuan Hsieh, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai, Ming-Lung Yu
Hepatitis C virus (HCV)-induced hepatic stress is associated with increased oxidative DNA damage and has been implicated in hepatic inflammation. However, HCV infection and replication are uneven and vary among individual hepatocytes. To investigate the effect of the viral load on host DNA damage, we used an Enhanced Yellow Fluorescent Protein gene (EYFP)-tagged HCV virus to distinguish between HCV intracellular high viral load (HVL) cells and low viral load (LVL) cells. The cell sorting efficiency was confirmed by the high expression of the HCV polyprotein...
2017: PloS One
https://www.readbyqxmd.com/read/28046013/homologous-recombination-defective-arabidopsis-mutants-exhibit-enhanced-sensitivity-to-abscisic-acid
#7
Sujit Roy, Kali Pada Das
Abscisic acid (ABA) acts as an important plant hormone in regulating various aspects of plant growth and developmental processes particularly under abiotic stress conditions. An increased ABA level in plant cells inhibits DNA replication and cell division, causing plant growth retardation. In this study, we have investigated the effects of ABA on the growth responses of some major loss-of-function mutants of DNA double-stand break (DSB) repair genes in Arabidopsis during seed germination and early stages of seedling growth for understanding the role of ABA in the induction of genome instability in plants...
2017: PloS One
https://www.readbyqxmd.com/read/28045896/a-signature-of-genomic-instability-resulting-from-deficient-replication-licensing
#8
Steven C Pruitt, Maochun Qin, Jianmin Wang, Dimiter Kunnev, Amy Freeland
Insufficient licensing of DNA replication origins has been shown to result in genome instability, stem cell deficiency, and cancers. However, it is unclear whether the DNA damage resulting from deficient replication licensing occurs generally or if specific sites are preferentially affected. To map locations of ongoing DNA damage in vivo, the DNAs present in red blood cell micronuclei were sequenced. Many micronuclei are the product of DNA breaks that leave acentromeric remnants that failed to segregate during mitosis and should reflect the locations of breaks...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28026186/the-use-of-graphene-and-its-derivatives-for-liquid-phase-transmission-electron-microscopy-of-radiation-sensitive-specimens
#9
Hoduk Cho, Matthew R Jones, Son C Nguyen, Matthew R Hauwiller, Alex Zettl, A Paul Alivisatos
One of the key challenges facing liquid-phase transmission electron microscopy (TEM) of biological specimens has been the damaging effects of electron beam irradiation. The strongly ionizing electron beam is known to induce radiolysis of surrounding water molecules, leading to the formation of reactive radical species. In this study, we employ DNA-assembled Au nanoparticle superlattices (DNA-AuNP superlattices) as a model system to demonstrate that graphene and its derivatives can be used to mitigate electron beam-induced damage...
December 28, 2016: Nano Letters
https://www.readbyqxmd.com/read/28018769/significance-of-interviral-recombination-as-novel-mechanism-for-extending-viral-disease-repertoire
#10
Edward M Johnson, Dianne C Daniel
The recent observation of interviral recombination between members of two distinct classes of DNA viruses has opened the gates to a new field of human disease development. In all cases studied thus far interviral recombination is a rare event that requires special circumstances for intracellular interaction of participating viral genomes. The rarity and special requirements do not detract from the potential clinical significance of resulting recombinants, as exemplified by recombination between JC viral and Epstein-Barr viral genomes...
October 2016: Brain Disorders & Therapy
https://www.readbyqxmd.com/read/28009302/rpa-stabilization-of-single-stranded-dna-is-critical-for-break-induced-replication
#11
Patrick Ruff, Roberto A Donnianni, Eleanor Glancy, Julyun Oh, Lorraine S Symington
DNA double-strand breaks (DSBs) are cytotoxic lesions that must be accurately repaired to maintain genome stability. Replication protein A (RPA) plays an important role in homology-dependent repair of DSBs by protecting the single-stranded DNA (ssDNA) intermediates formed by end resection and by facilitating Rad51 loading. We found that hypomorphic mutants of RFA1 that support intra-chromosomal homologous recombination are profoundly defective for repair processes involving long tracts of DNA synthesis, in particular break-induced replication (BIR)...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/27984746/mammalian-rad52-functions-in-break-induced-replication-repair-of-collapsed-dna-replication-forks
#12
Sotirios K Sotiriou, Irene Kamileri, Natalia Lugli, Konstantinos Evangelou, Caterina Da-Ré, Florian Huber, Laura Padayachy, Sebastien Tardy, Noemie L Nicati, Samia Barriot, Fena Ochs, Claudia Lukas, Jiri Lukas, Vassilis G Gorgoulis, Leonardo Scapozza, Thanos D Halazonetis
Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose depletion inhibited G1 to S phase progression when oncogenic cyclin E was overexpressed. RAD52, a gene dispensable for normal development in mice, was among the top hits. In cells in which fork collapse was induced by oncogenes or chemicals, the Rad52 protein localized to DRS foci...
December 15, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27976495/detection-of-dna-double-strand-breaks-by-pulsed-field-gel-electrophoresis
#13
Yuri Kawashima, Nahomi Yamaguchi, Rie Teshima, Hisashi Narahara, Yoshio Yamaoka, Hirofumi Anai, Yoshihiro Nishida, Katsuhiro Hanada
A DNA double-strand break (DSB) is one of the most cytotoxic DNA lesions because unrepaired DSBs cause chromosomal aberrations and cell death. Although many physiological DSBs occur at DNA replication sites, the molecular mechanisms underlying this remain poorly understood. There was therefore a need to develop a highly specific method to detect DSB fragments containing DNA replication sites. Here we investigated whether pulsed-field gel electrophoresis (PFGE) combined with visualization of DNA replication sites by immunoblotting using halogenized deoxyuridines, such as BrdU and IdU, was sufficient for this detection...
December 15, 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/27974207/dna-replication-origins-in-immunoglobulin-switch-regions-regulate-class-switch-recombination-in-an-r-loop-dependent-manner
#14
Eva-Maria Wiedemann, Mihaela Peycheva, Rushad Pavri
Class switch recombination (CSR) at the immunoglobulin heavy chain (IgH) locus generates antibody isotypes. CSR depends on double-strand breaks (DSBs) induced by activation-induced cytidine deaminase (AID). Although DSB formation and repair machineries are active in G1 phase, efficient CSR is dependent on cell proliferation and S phase entry; however, the underlying mechanisms are obscure. Here, we show that efficient CSR requires the replicative helicase, the Mcm complex. Mcm proteins are enriched at IgH switch regions during CSR, leading to assembly of facultative replication origins that require Mcm helicase function for productive CSR...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27940552/and-1-coordinates-with-ctip-for-efficient-homologous-recombination-and-dna-damage-checkpoint-maintenance
#15
Yali Chen, Hailong Liu, Haoxing Zhang, Changqing Sun, Zhaohua Hu, Qingsong Tian, Changmin Peng, Pei Jiang, Hui Hua, Xinzhi Li, Huadong Pei
To prevent genomic instability, cells respond to DNA lesions by blocking cell cycle progression and initiating DNA repair. Homologous recombination repair of DNA breaks requires CtIP-dependent resection of the DNA ends, which is thought to play a key role in activation of CHK1 kinase to induce the cell cycle checkpoint. But the mechanism is still not fully understood. Here, we establish that And-1, a replisome component, promotes DNA-end resection and DNA repair by homologous recombination. Mechanistically, And-1 interacts with CtIP and regulates CtIP recruitment to DNA damage sites...
December 9, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27938663/rnase-h-enables-efficient-repair-of-r-loop-induced-dna-damage
#16
Jeremy D Amon, Douglas Koshland
R-loops, three-stranded structures that form when transcripts hybridize to chromosomal DNA, are potent agents of genome instability. This instability has been explained by the ability of R-loops to induce DNA damage. Here, we show that persistent R-loops also compromise DNA repair. Depleting endogenous RNase H activity impairs R-loop removal in Saccharomyces cerevisiae, causing DNA damage that occurs preferentially in the repetitive ribosomal DNA locus (rDNA). We analyzed the repair kinetics of this damage and identified mutants that modulate repair...
December 10, 2016: ELife
https://www.readbyqxmd.com/read/27932446/topoisomerase-i-mediated-cleavage-at-unrepaired-ribonucleotides-generates-dna-double-strand-breaks
#17
Shar-Yin N Huang, Jessica S Williams, Mercedes E Arana, Thomas A Kunkel, Yves Pommier
Ribonuclease activity of topoisomerase I (Top1) causes DNA nicks bearing 2',3'-cyclic phosphates at ribonucleotide sites. Here, we provide genetic and biochemical evidence that DNA double-strand breaks (DSBs) can be directly generated by Top1 at sites of genomic ribonucleotides. We show that RNase H2-deficient yeast cells displayed elevated frequency of Rad52 foci, inactivation of RNase H2 and RAD52 led to synthetic lethality, and combined loss of RNase H2 and RAD51 induced slow growth and replication stress...
December 8, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27930670/ku-binding-on-telomeres-occurs-at-sites-distal-from-the-physical-chromosome-ends
#18
Mélanie V Larcher, Emeline Pasquier, R Stephen MacDonald, Raymund J Wellinger
The Ku complex binds non-specifically to DNA breaks and ensures repair via NHEJ. However, Ku is also known to bind directly to telomeric DNA ends and its presence there is associated with telomere capping, but avoiding NHEJ. How the complex discriminates between a DNA break and a telomeric extremity remains unknown. Our results using a tagged Ku complex, or a chromosome end capturing method, in budding yeast show that yKu association with telomeres can occur at sites distant from the physical end, on sub-telomeric elements, as well as on interstitial telomeric repeats...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27918542/the-role-of-break-induced-replication-in-large-scale-expansions-of-cag-n-ctg-n-repeats
#19
Jane C Kim, Samantha T Harris, Teresa Dinter, Kartik A Shah, Sergei M Mirkin
Expansions of (CAG)n/(CTG)n trinucleotide repeats are responsible for over a dozen neuromuscular and neurodegenerative disorders. Large-scale expansions are commonly observed in human pedigrees and may be explained by iterative small-scale events such as strand slippage during replication or repair DNA synthesis. Alternatively, a distinct mechanism may lead to a large-scale repeat expansion as a single step. To distinguish between these possibilities, we developed a novel experimental system specifically tuned to analyze large-scale expansions of (CAG)n/(CTG)n repeats in Saccharomyces cerevisiae...
January 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27911848/global-analysis-of-genomic-instability-caused-by-dna-replication-stress-in-saccharomyces-cerevisiae
#20
Dao-Qiong Zheng, Ke Zhang, Xue-Chang Wu, Piotr A Mieczkowski, Thomas D Petes
DNA replication stress (DRS)-induced genomic instability is an important factor driving cancer development. To understand the mechanisms of DRS-associated genomic instability, we measured the rates of genomic alterations throughout the genome in a yeast strain with lowered expression of the replicative DNA polymerase δ. By a genetic test, we showed that most recombinogenic DNA lesions were introduced during S or G2 phase, presumably as a consequence of broken replication forks. We observed a high rate of chromosome loss, likely reflecting a reduced capacity of the low-polymerase strains to repair double-stranded DNA breaks (DSBs)...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
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