IF 2.7 3区生物学

DNA Repair Pub Date : 2026-03-01 Epub Date: 2026-02-26 DOI: 10.1016/j.dnarep.2026.103929

Martin Lavin , A.M.R. Taylor , Yosef Shiloh

引用次数: 0

Sgs1 and Esc2 suppress chromosome translocations induced by a replication fork barrier in Saccharomyces cerevisiae Sgs1和Esc2抑制酿酒酵母复制叉屏障诱导的染色体易位。

IF 2.7 3区生物学

DNA Repair Pub Date : 2026-03-01 Epub Date: 2026-03-11 DOI: 10.1016/j.dnarep.2026.103930

Léa Marie , Marina K. Triplett , Iffat Ahmed , Lorraine S. Symington

{"title":"Sgs1 and Esc2 suppress chromosome translocations induced by a replication fork barrier in Saccharomyces cerevisiae","authors":"Léa Marie , Marina K. Triplett , Iffat Ahmed , Lorraine S. Symington","doi":"10.1016/j.dnarep.2026.103930","DOIUrl":"10.1016/j.dnarep.2026.103930","url":null,"abstract":"<div><div>Replication stress is recognized as a major cause of genomic instability in eukaryotes and is associated with various human pathologies, including cancer. To investigate the mechanisms driving gross chromosomal rearrangements in response to replication stress, we used the bacterial Tus/<em>Ter</em> barrier to engineer a site-specific replication fork block in the <em>Saccharomyces cerevisiae</em> genome. Surprisingly, we find that replication fork stalling adjacent to a region sharing homology with other chromosomes only modestly induces translocations in wild-type cells. However, the frequency of chromosome translocations is greatly increased in the absence of Sgs1 or Esc2. We show that the elevated frequency of Tus/<em>Ter</em>-induced translocations in <em>sgs1</em>Δ and <em>esc2</em>Δ mutants is completely dependent on <em>RAD51</em>, consistent with their formation by homologous recombination. In addition, we find that Exo1 nuclease contributes to the high frequency of chromosome translocations observed in <em>sgs1</em>Δ and <em>esc2</em>Δ cells, while the Mph1 translocase participates in replication stress-induced GCRs mostly in the absence of Esc2. Based on our findings, we propose that different factors contribute positively or negatively to the formation of chromosomal rearrangements associated with replication stress.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"159 ","pages":"Article 103930"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147482923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

B cell receptor stimulation inhibits class switch recombination through elevated DNA repair B细胞受体刺激通过提高DNA修复抑制类开关重组

IF 2.7 3区生物学

DNA Repair Pub Date : 2026-03-01 Epub Date: 2026-03-08 DOI: 10.1016/j.dnarep.2026.103931

Robert W. Maul , Rhonda L. McFleder , Zheng Cao , Darrell D. Norton , Jana Ridani , Philip Barbulescu , Alberto Martin , Javier M. Di Noia , Patricia J. Gearhart

{"title":"B cell receptor stimulation inhibits class switch recombination through elevated DNA repair","authors":"Robert W. Maul , Rhonda L. McFleder , Zheng Cao , Darrell D. Norton , Jana Ridani , Philip Barbulescu , Alberto Martin , Javier M. Di Noia , Patricia J. Gearhart","doi":"10.1016/j.dnarep.2026.103931","DOIUrl":"10.1016/j.dnarep.2026.103931","url":null,"abstract":"<div><div>Antibody diversity in B cells arises from the activity of activation-induced deaminase (AID), which introduces uracils into DNA of the immunoglobulin loci. The presence of uracil initiates a cascade of mutagenic events, resulting in somatic hypermutation and class switch recombination (CSR). To produce CSR, uracils are removed from DNA by uracil DNA glycosylase (UNG), resulting in formation of an abasic site, which is subsequently transformed into a double-stand break and promotes recombination to another constant gene. While the classical model indicates that B cells are activated when the IgM receptor binds antigen, stimulation of cells <em>ex vivo</em> with anti-IgM is insufficient for CSR. In fact, anti-IgM stimulation has a strong inhibitory effect on CSR when added together with lipopolysaccharide (LPS). To determine the mechanism of anti-IgM inhibition of CSR, we examined the known components required for CSR: AID and UNG. After stimulation with anti-IgM and LPS, AID was expressed and recruited to the immunoglobulin loci, and UNG levels increased and prevented uracil accumulation. We also linked the increased expression of UNG to the cell-cycle, as the presence of anti-IgM allowed cells to enter S-phase sooner. Therefore, for efficient CSR, AID-induced uracils must accumulate to sufficient levels before initiating S-phase, to provide more substrate for UNG and endonuclease to generate mutagenic strand breaks. If cell division occurs too early, as in the case of stimulation with anti-IgM and LPS, UNG is quickly upregulated and removes the uracils before they can accumulate, resulting in faithful DNA repair and less CSR.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"159 ","pages":"Article 103931"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147453614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evidence that MutSβ repairs indels generated by mispair initiated template slippage MutSβ修复由错配产生的缺陷的证据引发了模板滑移。

IF 2.7 3区生物学

DNA Repair Pub Date : 2026-03-01 Epub Date: 2026-03-12 DOI: 10.1016/j.dnarep.2026.103932

Scott A. Lujan, Alan B. Clark, Jessica S. Williams, Thomas A. Kunkel

{"title":"Evidence that MutSβ repairs indels generated by mispair initiated template slippage","authors":"Scott A. Lujan, Alan B. Clark, Jessica S. Williams, Thomas A. Kunkel","doi":"10.1016/j.dnarep.2026.103932","DOIUrl":"10.1016/j.dnarep.2026.103932","url":null,"abstract":"<div><div>This study examines the specificity of MutSβ dependent DNA mismatch repair (MMR) at the <em>URA3</em> reporter gene in <em>Saccharomyces cerevisiae</em>. Addition and deletion mutations containing multiple base changes are observed at elevated rates in <em>msh3∆</em> strains. This is consistent with a role for MutSβ in repairing multibase mismatches, such as those important in development of certain diseases and possibly including those made during Okazaki fragment maturation. Mutations containing single C-G base pair deletions are also observed at elevated rates in <em>msh3</em>∆ strains. These mutations are observed at still higher rates in <em>msh3</em>∆ strains with mutator variants of the three major replicases, implicating a defect in insertion/deletion repair during nuclear DNA replication. These deletions are observed at only a subset of detectable locations in <em>URA3</em> and they occur at higher rates in one of two orientations of <em>URA3</em> relative to the nearest replication origin. This subset of sites has a strong local DNA sequence context bias suggesting that the deletions are initiated by transient base•base mismatches which lead to template strand slippage, a type of transient initiator mutagenesis (TIM). We conclude that these mispair-initiated template slippage events require MMR via MutSβ before the next round of DNA synthesis to prevent deletion of an unpaired cytosine in the template strand.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"159 ","pages":"Article 103932"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147482836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dss1 facilitates Rad51 recruitment downstream of BRCA2/Brh2 in response to DNA damage Dss1在响应DNA损伤时促进BRCA2/Brh2下游的Rad51募集。

IF 2.7 3区生物学

DNA Repair Pub Date : 2026-02-01 Epub Date: 2026-01-22 DOI: 10.1016/j.dnarep.2026.103923

Louise Juhl , Linea Busch , Jonas Bagge , Ruiqi Xu , Milorad Kojic , Mira Milisavljevic , Vibe H. Oestergaard , William K. Holloman , Michael Lisby

{"title":"Dss1 facilitates Rad51 recruitment downstream of BRCA2/Brh2 in response to DNA damage","authors":"Louise Juhl , Linea Busch , Jonas Bagge , Ruiqi Xu , Milorad Kojic , Mira Milisavljevic , Vibe H. Oestergaard , William K. Holloman , Michael Lisby","doi":"10.1016/j.dnarep.2026.103923","DOIUrl":"10.1016/j.dnarep.2026.103923","url":null,"abstract":"<div><div>Homologous recombination (HR) is a major pathway for repair of DNA double-strand breaks (DSB), recovery of broken replication forks and formation of meiotic crossovers. HR provides a mechanism to precisely repair damaged DNA in a template-dependent process. The defining step in HR is homologous strand exchange directed by the RecA-related recombinase Rad51. BRCA2 and Brh2, the BRCA2 orthologue in <em>Ustilago maydis</em>, enable recombinational repair of DNA by controlling Rad51. In turn, Dss1, a small intrinsically disordered protein that binds to the C-terminal region of BRCA2/Brh2, regulates BRCA2/Brh2. In the present study, we dissect the interdependency of HR proteins for recruitment to DNA-damage induced foci using fluorescence microscopy and genetics. In <em>U. maydis</em>, Brh2 and Dss1 colocalize at DNA damage-induced foci. Dss1 recruitment to foci is dependent on interaction with full-length Brh2 and Dss1-Brh2 interaction is required for resistance to DNA damage. Further, Dss1 is required for Rad51 and Rec2 focus formation. Interestingly, we find that Rad52 is required for Brh2, Rec2 and Dss1 focus formation. In avian DT40 cells, we likewise show that endogenously tagged DSS1 redistributes into subnuclear foci in response to DNA damaging agents. However, DSS1 foci rarely colocalize with BRCA2 foci. Finally, Dss1 focus formation is inhibited by treatment with the proteasome inhibitor MG132, in both <em>U. maydis</em> and DT40 cells, suggesting a role of ubiquitin in homology-dependent repair.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"158 ","pages":"Article 103923"},"PeriodicalIF":2.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146069330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Editorial: DNA crosslink repair: From molecules to mankind 社论：DNA交联修复：从分子到人类。

IF 2.7 3区生物学

DNA Repair Pub Date : 2026-02-01 Epub Date: 2026-01-29 DOI: 10.1016/j.dnarep.2026.103927

Penny Jeggo , Puck Knipscheer , Peter J. McHugh

引用次数: 0

Tribute to life and science of Grigory (Gosha) Dianov 向格里戈里·迪亚诺夫的生命和科学致敬。

IF 2.7 3区生物学

DNA Repair Pub Date : 2026-02-01 Epub Date: 2026-01-30 DOI: 10.1016/j.dnarep.2026.103925

Alexander V. Mazin , Andrei Kuzminov , Murat Saparbaev , Svetlana Khoronenkova , Jason Parsons , Sarah Allinson

引用次数: 0

Search, verify and excise-lesion recognition in NER 在NER中搜索、验证和切除病变识别

IF 2.7 3区生物学

DNA Repair Pub Date : 2026-02-01 Epub Date: 2026-01-12 DOI: 10.1016/j.dnarep.2026.103922

Jochen Kuper, Caroline Kisker

引用次数: 0

A special issue: DNA damage response in disease and therapy 特刊：疾病和治疗中的DNA损伤反应。

IF 2.7 3区生物学

DNA Repair Pub Date : 2026-02-01 Epub Date: 2026-01-22 DOI: 10.1016/j.dnarep.2026.103924

Guo-Min Li, Zhao-Qi Wang

引用次数: 0

DNA Repair Special Issue: Genome maintenance pathways in cancer - etiology, biomarkers and targets DNA修复特刊：癌症的基因组维持途径——病因学、生物标志物和靶标。

IF 2.7 3区生物学

DNA Repair Pub Date : 2026-02-01 Epub Date: 2026-01-29 DOI: 10.1016/j.dnarep.2026.103926

Robert W. Sobol , Gianluca Tell

引用次数: 0

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