DNA Repair最新文献_第3页

Werner helicase as a therapeutic target in mismatch repair deficient colorectal cancer 维尔纳解旋酶作为错配修复缺陷结直肠癌的治疗靶点

IF 3 3区生物学

DNA Repair Pub Date : 2025-04-03 DOI: 10.1016/j.dnarep.2025.103831

Suisui Hao , Zhaojin Liu , Heinz-Josef Lenz , Jian Yu , Lin Zhang

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The replication stress response: Mechanisms and functions 复制应激反应：机制和功能

IF 3 3区生物学

DNA Repair Pub Date : 2025-04-01 DOI: 10.1016/j.dnarep.2025.103834

Alberto Ciccia, Alessandro Vindigni

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Transport of DNA repair proteins to the cell nucleus by the classical nuclear importin pathway – a structural overview DNA修复蛋白转运到细胞核的经典核输入蛋白途径-结构概述

IF 3 3区生物学

DNA Repair Pub Date : 2025-03-23 DOI: 10.1016/j.dnarep.2025.103828

Marcos R.M. Fontes , Fábio F. Cardoso , Bostjan Kobe

{"title":"Transport of DNA repair proteins to the cell nucleus by the classical nuclear importin pathway – a structural overview","authors":"Marcos R.M. Fontes , Fábio F. Cardoso , Bostjan Kobe","doi":"10.1016/j.dnarep.2025.103828","DOIUrl":"10.1016/j.dnarep.2025.103828","url":null,"abstract":"<div><div>DNA repair is a crucial biological process necessary to address damage caused by both endogenous and exogenous agents, with at least five major pathways recognized as central to this process. In several cancer types and other diseases, including neurodegenerative disorders, DNA repair mechanisms are often disrupted or dysregulated. Despite the diversity of these proteins and their roles, they all share the common requirement of being imported into the cell nucleus to perform their functions. Therefore, understanding the nuclear import of these proteins is essential for comprehending their roles in cellular processes. The first and best-characterized nuclear targeting signal is the classical nuclear localization sequence (NLS), recognized by importin-α (Impα). Several structural and affinity studies have been conducted on complexes formed between Impα and NLSs from DNA repair proteins, although these represent only a fraction of all known DNA repair proteins. These studies have significantly advanced our understanding of the nuclear import process of DNA repair proteins, often revealing unexpected results that challenge existing literature and computational predictions. Despite advances in computational, biochemical, and cellular assays, structural methods – particularly crystallography and in-solution biophysical approaches – continue to play a critical role in providing insights into molecular events operating in biological pathways. In this review, we aim to summarize experimental structural and affinity studies involving Impα and NLSs from DNA repair proteins, with the goal of furthering our understanding of the function of these essential proteins.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"149 ","pages":"Article 103828"},"PeriodicalIF":3.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714593","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}

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Modulation of OGG1 enzymatic activities by small molecules, promising tools and current challenges 小分子调控OGG1酶活性，有前途的工具和当前的挑战

IF 3 3区生物学

DNA Repair Pub Date : 2025-03-16 DOI: 10.1016/j.dnarep.2025.103827

Xavier Renaudin , Anna Campalans

{"title":"Modulation of OGG1 enzymatic activities by small molecules, promising tools and current challenges","authors":"Xavier Renaudin , Anna Campalans","doi":"10.1016/j.dnarep.2025.103827","DOIUrl":"10.1016/j.dnarep.2025.103827","url":null,"abstract":"<div><div>Oxidative DNA damage, resulting from endogenous cellular processes and external sources plays a significant role in mutagenesis, cancer progression, and the pathogenesis of neurological disorders. Base Excision Repair (BER) is involved in the repair of base modifications such as oxidations or alkylations as well as single strand breaks. The DNA glycosylase OGG1, initiates the BER pathway by the recognition and excision of 8oxoG, the most common oxidative DNA lesion, in both nuclear and mitochondrial DNA. Beyond DNA repair, OGG1 modulates transcription, particularly pro-inflammatory genes, linking oxidative DNA damage to broader biological processes like inflammation and aging. In cancer therapy, BER inhibition has emerged as a promising strategy to enhance treatment efficacy. Targeting OGG1 sensitizes cells to chemotherapies, radiotherapies, and PARP inhibitors, presenting opportunities to overcome therapy resistance. Additionally, OGG1 activators hold potential in mitigating oxidative damage associated with aging and neurological disorders. This review presents the development of several inhibitors and activators of OGG1 and how they have contributed to advance our knowledge in the fundamental functions of OGG1. We also discuss the new opportunities they provide for clinical applications in treating cancer, inflammation and neurological disorders. Finally, we also highlight the challenges in targeting OGG1, particularly regarding the off-target effects recently reported for some inhibitors and how we can overcome these limitations.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"149 ","pages":"Article 103827"},"PeriodicalIF":3.0,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687722","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}

引用次数: 0

Temporal and spatial dynamics of DNA double-strand break repair centers DNA双链断裂修复中心的时空动力学

IF 3 3区生物学

DNA Repair Pub Date : 2025-03-13 DOI: 10.1016/j.dnarep.2025.103825

Junyi Chen , Wenkang Zhang , Yuqi Ma , Xueqing Yan , Yugang Wang , Qi Ouyang , Min Wu , Gen Yang

引用次数: 0

Repair pathway coordination from gap filling by polβ and subsequent nick sealing by LIG1 or LIG3α governs BER efficiency at the downstream steps 由polβ填补缺口和随后由LIG1或LIG3α闭合缺口的修复途径协调控制下游步骤的BER效率

IF 3 3区生物学

DNA Repair Pub Date : 2025-03-10 DOI: 10.1016/j.dnarep.2025.103826

Melike Çağlayan

{"title":"Repair pathway coordination from gap filling by polβ and subsequent nick sealing by LIG1 or LIG3α governs BER efficiency at the downstream steps","authors":"Melike Çağlayan","doi":"10.1016/j.dnarep.2025.103826","DOIUrl":"10.1016/j.dnarep.2025.103826","url":null,"abstract":"<div><div>Base excision repair (BER) is the critical mechanism for preventing mutagenic and lethal consequences of single base lesions generated by endogenous factors or exposure to environmental hazards. BER pathway involves multi-step enzymatic reactions that require a tight coordination between repair proteins to transfer DNA intermediates in an orderly manner. Though often considered an accurate process, the BER can contribute to genome instability if normal coordination between gap filling by DNA polymerase (pol) β and subsequent nick sealing by DNA ligase 1 (LIG1) or DNA ligase 3α (LIG3α) breaks down at the downstream steps. Our studies demonstrated that an inaccurate DNA ligation by LIG1/LIG3α, stemming from an uncoordinated repair with polβ, leads to a range of deviations from canonical BER pathway, faulty repair events, and formation of deleterious DNA intermediates. Furthermore, X-ray repair cross-complementing protein 1 (XRCC1), as a scaffolding factor, enhances the processivity of downstream steps, and the DNA-end processing enzymes, Aprataxin (APTX), Flap-Endonuclease 1 (FEN1), and AP-Endonuclease 1 (APE1), play critical roles for cleaning of ligase failure products and proofreading of polβ errors in coordination with BER ligases. Overall, our studies contribute to understanding of how a multi-protein repair complex interplay at the final steps to maintain the repair efficiency.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"148 ","pages":"Article 103826"},"PeriodicalIF":3.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609266","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}

引用次数: 0

Targeting dePARylation in cancer therapy 靶向脱脂血酶在癌症治疗中的应用

IF 3 3区生物学

DNA Repair Pub Date : 2025-03-05 DOI: 10.1016/j.dnarep.2025.103824

Peng Li , Duo Wu , Xiaochun Yu

引用次数: 0

Advances in diagnostic and therapeutic applications of mismatch repair loss in cancer 错配修复缺失在癌症诊断和治疗中的应用进展

IF 3 3区生物学

DNA Repair Pub Date : 2025-03-01 DOI: 10.1016/j.dnarep.2025.103822

JT DeWitt , D. Jimenez-Tovar , A. Mazumder , S. Haricharan

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RNA damage and its implications in genome stability RNA损伤及其对基因组稳定性的影响

IF 3 3区生物学

DNA Repair Pub Date : 2025-03-01 DOI: 10.1016/j.dnarep.2025.103821

Mustapha Olatunji , Yuan Liu

{"title":"RNA damage and its implications in genome stability","authors":"Mustapha Olatunji , Yuan Liu","doi":"10.1016/j.dnarep.2025.103821","DOIUrl":"10.1016/j.dnarep.2025.103821","url":null,"abstract":"<div><div>Endogenous and environmental stressors can damage DNA and RNA to compromise genome and transcriptome stability and integrity in cells, leading to genetic instability and diseases. Recent studies have demonstrated that RNA damage can also modulate genome stability via RNA-templated DNA synthesis, suggesting that it is essential to maintain RNA integrity for the sustainment of genome stability. However, little is known about RNA damage and repair and their roles in modulating genome stability. Current efforts have mainly focused on revealing RNA surveillance pathways that detect and degrade damaged RNA, while the critical role of RNA repair is often overlooked. Due to their abundance and susceptibility to nucleobase damaging agents, it is essential for cells to evolve robust RNA repair mechanisms that can remove RNA damage, maintaining RNA integrity during gene transcription. This is supported by the discovery of the alkylated RNA nucleobase repair enzyme human AlkB homolog 3 that can directly remove the methyl group on damaged RNA nucleobases, predominantly in the nucleus of human cells, thereby restoring the integrity of the damaged RNA nucleobases. This is further supported by the fact that several DNA repair enzymes can also process RNA damage. In this review, we discuss RNA damage and its effects on cellular function, DNA repair, genome instability, and potential RNA damage repair mechanisms. Our review underscores the necessity for future research on RNA damage and repair and their essential roles in modulating genome stability.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"147 ","pages":"Article 103821"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551630","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

The hidden elephant: Modified abasic sites and their consequences 隐藏的大象：修改的基本站点及其后果

IF 3 3区生物学

DNA Repair Pub Date : 2025-02-28 DOI: 10.1016/j.dnarep.2025.103823

Anna V. Yudkina , Dmitry O. Zharkov

{"title":"The hidden elephant: Modified abasic sites and their consequences","authors":"Anna V. Yudkina , Dmitry O. Zharkov","doi":"10.1016/j.dnarep.2025.103823","DOIUrl":"10.1016/j.dnarep.2025.103823","url":null,"abstract":"<div><div>Abasic, or apurinic/apyrimidinic sites (AP sites) are among the most abundant DNA lesions, appearing in DNA both through spontaneous base loss and as intermediates of base excision DNA repair. Natural aldehydic AP sites have been known for decades and their interaction with the cellular replication, transcription and repair machinery has been investigated in detail. Oxidized AP sites, produced by free radical attack on intact nucleotides, received much attention recently due to their ability to trap DNA repair enzymes and chromatin structural proteins such as histones. In the past few years, it became clear that the reactive nature of aldehydic and oxidized AP sites produces a variety of modifications, including AP site–protein and AP site–peptide cross-links, adducts with small molecules of metabolic or xenobiotic origin, and AP site-mediated interstrand DNA cross-links. The diverse chemical nature of these common-origin lesions is reflected in the wide range of their biological consequences. In this review, we summarize the data on the mechanisms of modified AP sites generation, their abundance, the ability to block DNA polymerases or cause nucleotide misincorporation, and the pathways of their repair.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"148 ","pages":"Article 103823"},"PeriodicalIF":3.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562469","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