DNA Repair最新文献

{"title":"Lawrence H. Thompson: A life of bikes, birds, and DNA repair (1941–2024)","authors":"Keith W. Caldecott","doi":"10.1016/j.dnarep.2025.103813","DOIUrl":"10.1016/j.dnarep.2025.103813","url":null,"abstract":"","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"146 ","pages":"Article 103813"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070378","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}

{"title":"Single-molecule toxicogenomics: Optical genome mapping of DNA-damage in nanochannel arrays","authors":"Tahir Detinis Zur ,&nbsp;Sapir Margalit ,&nbsp;Jonathan Jeffet ,&nbsp;Assaf Grunwald ,&nbsp;Sivan Fishman ,&nbsp;Zuzana Tulpová ,&nbsp;Yael Michaeli ,&nbsp;Jasline Deek ,&nbsp;Yuval Ebenstein","doi":"10.1016/j.dnarep.2025.103808","DOIUrl":"10.1016/j.dnarep.2025.103808","url":null,"abstract":"<div><div>Quantitative genomic mapping of DNA damage may provide insights into the underlying mechanisms of damage and repair. Sequencing based approaches are bound to the limitations of PCR amplification bias and read length which hamper both the accurate quantitation of damage events and the ability to map them to structurally complex genomic regions. Optical Genome mapping in arrays of parallel nanochannels allows physical extension and genetic profiling of millions of long genomic DNA fragments, and has matured to clinical utility for characterization of complex structural aberrations in cancer genomes. Here we present a new mapping modality, Repair-Assisted Damage Detection - Optical Genome Mapping (RADD-OGM), a method for single-molecule level mapping of DNA damage on a genome-wide scale. Leveraging ultra-long reads to assemble the complex structure of a sarcoma cell-line genome, we mapped the genomic distribution of oxidative DNA damage, identifying regions more susceptible to DNA oxidation. We also investigated DNA repair by allowing cells to repair chemically induced DNA damage, pinpointing locations of concentrated repair activity, and highlighting variations in repair efficiency. Our results showcase the potential of the method for toxicogenomic studies, mapping the effect of DNA damaging agents such as drugs and radiation, as well as following specific DNA repair pathways by selective induction of DNA damage. The facile integration with optical genome mapping enables performing such analyses even in highly rearranged genomes such as those common in many cancers, a challenging task for sequencing-based approaches.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"146 ","pages":"Article 103808"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018817","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}

{"title":"Active genome integrity","authors":"Sukesh R. Bhaumik","doi":"10.1016/j.dnarep.2025.103816","DOIUrl":"10.1016/j.dnarep.2025.103816","url":null,"abstract":"","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"146 ","pages":"Article 103816"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349370","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}

{"title":"To divide or not to divide? NAC8 (SOG1) as a key regulator of DNA damage response in barley (Hordeum vulgare L.)","authors":"Miriam Szurman-Zubrzycka ,&nbsp;Anna Kocjan ,&nbsp;Emilia Spałek ,&nbsp;Monika Gajecka ,&nbsp;Paulina Jędrzejek ,&nbsp;Małgorzata Nawrot ,&nbsp;Iwona Szarejko ,&nbsp;Jolanta Kwasniewska","doi":"10.1016/j.dnarep.2025.103810","DOIUrl":"10.1016/j.dnarep.2025.103810","url":null,"abstract":"<div><div>We identified several new TILLING mutants of barley (<em>Hordeum vulgare</em> L.) with missense mutations in the <em>HvNAC8</em> gene, a homolog of the <em>SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1)</em> gene in <em>Arabidopsis thaliana</em>. In Arabidopsis, SOG1 is the primary regulator of the DNA Damage Response (DDR) pathway. We aimed to transfer this knowledge to barley, an agriculturally important crop. Our detailed analysis of the <em>hvnac8.k</em> mutant revealed an impaired DDR pathway. The <em>hvnac8.k</em> mutant accumulates DNA damage under genotoxic stress induced by zeocin, but it also shows increased DNA damage under normal growth conditions. Despite this, the frequency of dividing cells in the root meristem of the mutant treated with zeocin is much less affected than in the wild type. This suggests that the mutant bypasses the typical DDR regulation, where cell division is halted to allow DNA repair following damage. We also analyzed our mutant under aluminum (Al³⁺) stress. Aluminum ions, present in acidic soils that constitute approximately 50 % of arable land, are a common stressor that significantly reduce barley yield. Al³ ⁺ is known to cause DNA damage and activate DDR. Consequently, we aimed to assess whether the <em>hvnac8.k</em> phenotype could confer a beneficial effect under aluminum stress, a widespread agronomic challenge. Our findings suggest that modulation of the DDR pathway has the potential to improve aluminum tolerance in barley.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"146 ","pages":"Article 103810"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Ataxia-telangiectasia mutated (ATM) is the most important gene for repairing the DNA in Myelodysplastic Neoplasm","authors":"Ronald Feitosa Pinheiro ,&nbsp;João Vitor Caetano Goes ,&nbsp;Leticia Rodrigues Sampaio ,&nbsp;Roberta Taiane Germano de Oliveira ,&nbsp;Sheila Coelho Soares Lima ,&nbsp;Cristiana Libardi Miranda Furtado ,&nbsp;Daniela de Paula Borges ,&nbsp;Marilia Braga Costa ,&nbsp;Cristiane da Silva Monte ,&nbsp;Natalia Feitosa Minete ,&nbsp;Silvia Maria Meira Magalhães ,&nbsp;Howard Lopes Ribeiro Junior","doi":"10.1016/j.dnarep.2024.103803","DOIUrl":"10.1016/j.dnarep.2024.103803","url":null,"abstract":"<div><div>Myelodysplastic Neoplasm (MDS) is a cancer associated with aging, often leading to acute myeloid leukemia (AML). One of its hallmarks is hypermethylation, particularly in genes responsible for DNA repair. This study aimed to evaluate the methylation and mutation status of DNA repair genes (single-strand - <em>XPA, XPC, XPG, CSA, CSB</em> and double-strand - <em>ATM, BRCA1, BRCA2, LIG4, RAD51</em>) in MDS across three patient cohorts (Cohort A-56, Cohort B-100, Cohort C-76), using methods like pyrosequencing, real-time PCR, immunohistochemistry, and mutation screening. Results showed that <em>XPA</em> had higher methylation in low-risk MDS compared to high-risk MDS. For double-strand repair genes, <em>ATM</em> displayed higher methylation in patients who transformed to AML (p = 0.016). <em>ATM</em> gene expression was downregulated in MDS compared to controls (p = 0.042). When patients were classified according to the WHO 2022 guidelines, <em>ATM</em> expression progressively decreased from low-risk subtypes (e.g., Hypoplastic MDS) to high-risk MDS and AML. Patients who transformed to AML had a higher 5mC/5hmC ratio compared to those who didn’t (p = 0.045). Additionally, poor cytogenetic risk patients had higher tissue methylation scores than those with good risk (p = 0.035). Analysis using the cBioPortal platform identified <em>ATM</em> as the most frequently mutated DNA repair gene, with various mutations, such as frameshift and missense, most of which were classified as oncogenic. The findings suggest that <em>ATM</em> is frequently silenced or downregulated in MDS due to methylation or mutations, contributing to the progression to AML. This highlights <em>ATM</em>'s potential role in the disease’s advancement and as a target for future therapeutic strategies.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"146 ","pages":"Article 103803"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061755","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}

{"title":"Contents of Previous 3 Special Issues in this Series of Perspectives","authors":"","doi":"10.1016/j.dnarep.2025.103806","DOIUrl":"10.1016/j.dnarep.2025.103806","url":null,"abstract":"","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"146 ","pages":"Article 103806"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973951","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}

{"title":"Cutting edge perspectives in genome maintenance XI","authors":"Penelope Ann Jeggo","doi":"10.1016/j.dnarep.2025.103805","DOIUrl":"10.1016/j.dnarep.2025.103805","url":null,"abstract":"","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"146 ","pages":"Article 103805"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967584","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}

{"title":"The interplay between chromatin remodeling and DNA double-strand break repair: Implications for cancer biology and therapeutics","authors":"Liujun He ,&nbsp;Jaeyoung Moon ,&nbsp;Chenghui Cai ,&nbsp;Yalan Hao ,&nbsp;Hyorin Lee ,&nbsp;Wootae Kim ,&nbsp;Fei Zhao ,&nbsp;Zhenkun Lou","doi":"10.1016/j.dnarep.2025.103811","DOIUrl":"10.1016/j.dnarep.2025.103811","url":null,"abstract":"<div><div>Proper chromatin remodeling is crucial for many cellular physiological processes, including the repair of DNA double-strand break (DSB). While the mechanism of DSB repair is well understood, the connection between chromatin remodeling and DSB repair remains incompletely elucidated. In this review, we aim to highlight recent studies demonstrating the close relationship between chromatin remodeling and DSB repair. We summarize the impact of DSB repair on chromatin, including nucleosome arrangement, chromatin organization, and dynamics, and conversely, the role of chromatin architecture in regulating DSB repair. Additionally, we also summarize the contribution of chromatin remodeling complexes to cancer biology through DNA repair and discuss their potential as therapeutic targets for cancer.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"146 ","pages":"Article 103811"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small-molecule activator of SMUG1 enhances repair of pyrimidine lesions in DNA","authors":"Yixuan Gao ,&nbsp;Lisa McPherson ,&nbsp;Shanthi Adimoolam ,&nbsp;Samyuktha Suresh ,&nbsp;David L. Wilson ,&nbsp;Ishani Das ,&nbsp;Elizabeth R. Park ,&nbsp;Christine S.C. Ng ,&nbsp;Yong Woong Jun ,&nbsp;James M. Ford ,&nbsp;Eric T. Kool","doi":"10.1016/j.dnarep.2025.103809","DOIUrl":"10.1016/j.dnarep.2025.103809","url":null,"abstract":"<div><div>A potentially promising approach to targeted cancer prevention in genetically at-risk populations is the pharmacological upregulation of DNA repair pathways. SMUG1 is a base excision repair enzyme that ameliorates adverse genotoxic and mutagenic effects of hydrolytic and oxidative damage to pyrimidines. Here we describe the discovery and initial cellular activity of a small-molecule activator of SMUG1. Screening of a kinase inhibitor library and iterative rounds of structure-activity relationship studies produced compound <strong>40</strong> (SU0547), which activates SMUG1 by as much as 350 ± 60 % <em>in vitro</em> at 100 nM, with an AC₅₀ of 4.3 ± 1.1 µM. To investigate the effect of compound <strong>40</strong> on endogenous SMUG1, we performed <em>in vitro</em> cell-based experiments with 5-hydroxymethyl-2’-deoxyuridine (5-hmdU), a pyrimidine oxidation product that is selectively removed by SMUG1. In several human cell lines, compound <strong>40</strong> at 3–5 µM significantly reduces the cytotoxicity of 5-hmdU and decreases levels of double-strand breaks induced by the damaged nucleoside. We conclude that the SMUG1 activator compound <strong>40</strong> is a useful tool to study the mechanisms of 5-hmdU toxicity and the potentially beneficial effects of suppressing damage to pyrimidines in cellular DNA.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"146 ","pages":"Article 103809"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070379","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}

{"title":"DNA repair pathways in the mitochondria","authors":"Dillon E. King,&nbsp;William C. Copeland","doi":"10.1016/j.dnarep.2025.103814","DOIUrl":"10.1016/j.dnarep.2025.103814","url":null,"abstract":"<div><div>Mitochondria contain their own small, circular genome that is present in high copy number. The mitochondrial genome (mtDNA) encodes essential subunits of the electron transport chain. Mutations in the mitochondrial genome are associated with a wide range of mitochondrial diseases and the maintenance and replication of mtDNA is crucial to cellular health. Despite the importance of maintaining mtDNA genomic integrity, fewer DNA repair pathways exist in the mitochondria than in the nucleus. However, mitochondria have numerous pathways that allow for the removal and degradation of DNA damage that may prevent accumulation of mutations. Here, we briefly review the DNA repair pathways present in the mitochondria, sources of mtDNA mutations, and discuss the passive role that mtDNA mutagenesis may play in cancer progression.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"146 ","pages":"Article 103814"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143140725","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}