IF 2.7 3区生物学

DNA Repair Pub Date : 2025-10-01 DOI: 10.1016/j.dnarep.2025.103899

Xingkai He , Feng Chen , Linmin Zhou , Yuanqing Sun , Qi Liu , Weicheng Chen , Luyao Zhu , Jun Zhang , Wei-Guo Zhu

{"title":"The comet assay: A contemporary approach for detecting genomic instability","authors":"Xingkai He , Feng Chen , Linmin Zhou , Yuanqing Sun , Qi Liu , Weicheng Chen , Luyao Zhu , Jun Zhang , Wei-Guo Zhu","doi":"10.1016/j.dnarep.2025.103899","DOIUrl":"10.1016/j.dnarep.2025.103899","url":null,"abstract":"<div><div>The comet assay has evolved into a high-resolution, multifunctional technique for evaluating DNA damage, repair capacity, and epigenetic modifications. Over the past fifteen years, significant advancements-including the enzyme-modified comet assays (EMCA), Comet-FISH, and high-throughput platforms have substantially expanded its analytical capabilities. Specialized formats like the Flash comet assay and the BrdU comet assay further enhance the discrimination of DNA strand break types and replication-associated damage. Despite these innovations, issues related to standardization, reproducibility, and inter-laboratory consistency remain. Initiatives such as the Minimum Information for Reporting Comet Assay (MIRCA) guidelines, alongside the integration of automated imaging and machine learning, are being implemented to address these challenges. With its growing applications in environmental toxicology, biomonitoring, and clinical research, the comet assay is increasingly recognized as a key tool in precision toxicology and personalized medicine. This review highlights major technical developments and emerging applications of the comet assay over the past fifteen years, discusses sources of experimental variability and strategies for optimization, and provides an update on current laboratory protocols for assessing DNA damage induced by genotoxic agents.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"154 ","pages":"Article 103899"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214977","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

PARP enzyme synthesis of protein-free poly(ADP-ribose): Implications for DNA damage signaling and repair 无蛋白聚核糖（adp -核糖）的PARP酶合成：对DNA损伤信号传导和修复的意义

IF 2.7 3区生物学

DNA Repair Pub Date : 2025-10-01 DOI: 10.1016/j.dnarep.2025.103898

Marie-France Langelier, John M. Pascal

引用次数: 0

Mechanistic insights into RAD51-mediated nucleosome binding and remodeling in homologous recombination 同源重组中rad51介导的核小体结合和重塑的机制研究。

IF 2.7 3区生物学

DNA Repair Pub Date : 2025-09-13 DOI: 10.1016/j.dnarep.2025.103891

Takuro Shioi , Suguru Hatazawa , Yoshimasa Takizawa , Hitoshi Kurumizaka

{"title":"Mechanistic insights into RAD51-mediated nucleosome binding and remodeling in homologous recombination","authors":"Takuro Shioi , Suguru Hatazawa , Yoshimasa Takizawa , Hitoshi Kurumizaka","doi":"10.1016/j.dnarep.2025.103891","DOIUrl":"10.1016/j.dnarep.2025.103891","url":null,"abstract":"<div><div>Eukaryotic cells organize their genomic DNA into chromatin to achieve both compact packaging and precise regulation of essential processes, including DNA repair. Depending on the type of damage, distinct repair pathways are activated through the targeted recruitment of repair factors to chromatin. RAD51 is the central recombinase in homologous recombination (HR) and forms nucleoprotein filaments, but its mode of chromatin engagement has remained elusive. In this review, we summarize recent progress in the structural and biochemical understanding of DNA repair within chromatin, with a particular focus on RAD51 and its role in HR. Specifically, we review newly determined cryo-electron microscopy (cryo-EM) structures of RAD51 bound to nucleosomes, revealing how RAD51 assembles on chromatin, recognizes DNA damage sites, and remodels nucleosomes into filamentous intermediates. We summarize current insights into how HR-associated proteins regulate RAD51 activity on chromatin, ensuring the fidelity of each step in HR. We conclude by outlining future directions for elucidating the downstream mechanisms of RAD51-mediated HR in the chromatin context.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"154 ","pages":"Article 103891"},"PeriodicalIF":2.7,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088633","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

Editors’ note Penny Jeggo and Bennett Van Houten 编者按潘妮·杰戈和班尼特·范·豪顿。

IF 2.7 3区生物学

DNA Repair Pub Date : 2025-09-01 DOI: 10.1016/j.dnarep.2025.103862

Penny Jeggo, Bennett Van Houten

引用次数: 0

Corrigendum to “Unveiling cGAS mechanisms: Insights into DNA damage and immune sensing in cancer” [DNA Repair 152 (2025) 103868] “揭开cGAS机制：对癌症中DNA损伤和免疫感知的见解”[DNA修复152(2025)103868]的更正。

IF 2.7 3区生物学

DNA Repair Pub Date : 2025-09-01 DOI: 10.1016/j.dnarep.2025.103878

Min-Guk Cho , Gaorav P. Gupta

引用次数: 0

The B cell dilemma: Diversity or fidelity? B细胞的困境：多样性还是保真性？

IF 2.7 3区生物学

DNA Repair Pub Date : 2025-09-01 DOI: 10.1016/j.dnarep.2025.103888

Maria Berruezo-Llacuna , Eleni Kabrani , Michela Di Virgilio

{"title":"The B cell dilemma: Diversity or fidelity?","authors":"Maria Berruezo-Llacuna , Eleni Kabrani , Michela Di Virgilio","doi":"10.1016/j.dnarep.2025.103888","DOIUrl":"10.1016/j.dnarep.2025.103888","url":null,"abstract":"<div><div>The ability of B lymphocytes to diversify immunoglobulin (<em>Ig</em>) genes is central to the generation of high-affinity, class-switched antibodies and the establishment of effective humoral immunity. This diversification is achieved through three DNA remodeling processes that occur at defined stages of B cell development and maturation: V(D)J recombination, somatic hypermutation (SHM), and class switch recombination (CSR). These reactions all rely on the induction of programmed DNA lesions at <em>Ig</em> genes and their productive resolution by ubiquitous DNA repair pathways. However, such physiological sources of genotoxic stress render B cells vulnerable to genome instability, including mutations and chromosomal translocations that drive malignancies. Therefore, B cells have evolved complex regulatory networks that ensure efficient <em>Ig</em> gene diversification while minimizing the risk of unproductive or deleterious repair outcomes. In this review, we integrate foundational studies with recent mechanistic advances to outline how B cells exploit, coordinate, and constrain DNA repair to balance immune receptor diversification with the preservation of genome integrity.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"153 ","pages":"Article 103888"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144989057","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

Contributions of DNA double strand break repair pathways to DNA crosslink repair DNA双链断裂修复途径对DNA交联修复的贡献

IF 2.7 3区生物学

DNA Repair Pub Date : 2025-09-01 DOI: 10.1016/j.dnarep.2025.103889

Gerarda van de Kamp , Israel Tojal da Silva , Sander Barnhoorn , Roland Kanaar , Jeroen Essers

{"title":"Contributions of DNA double strand break repair pathways to DNA crosslink repair","authors":"Gerarda van de Kamp , Israel Tojal da Silva , Sander Barnhoorn , Roland Kanaar , Jeroen Essers","doi":"10.1016/j.dnarep.2025.103889","DOIUrl":"10.1016/j.dnarep.2025.103889","url":null,"abstract":"<div><div>DNA crosslink-inducing drugs are widely used in clinical settings for treatment of solid tumors. Double strand breaks (DSBs) that arise during interstrand crosslink (ICL) repair are crucial determinants of the therapeutic response, as they lead to cell death if not repaired. DSBs can be repaired through non-homologous end joining (NHEJ), theta-mediated end joining (TMEJ), and homologous recombination (HR). HR is considered a major pathway for repairing DSBs induced during ICL repair. In this study, we examine the roles of NHEJ, TMEJ, and HR in ICL repair using mouse embryonic stem (mES) cells. We show that DNA-PK<sub>cs</sub>-deficient mES cells are resistant to the crosslinkers mitomycin C (MMC), cisplatin and carboplatin, contrasting with the increased sensitivity observed in mES cells lacking Rad54. Furthermore, the absence of DNA-PK<sub>cs</sub> correlates with enhanced HR activity, as evidenced by an increased number of Rad54 foci following MMC treatment. The combined knock-outof DNA-PK<sub>cs</sub> and Rad54 reduces sensitivity to crosslinkers compared to cells lacking only Rad54, suggesting the involvement of another DSB repair pathway besides HR. We found that TMEJ deficiency can sensitize cells to cisplatin, particularly in those lacking NHEJ and HR repair. This suggests that TMEJ contributes to cell survival following cisplatin treatment. In clinical settings, higher <em>PRKDC</em> expression correlates with poorer survival, while elevated <em>RAD54L</em> and <em>POLQ</em> expression correlates with better survival in cisplatin-treated cervical and head and neck cancers. These findings reflect the opposing roles of NHEJ versus HR and TMEJ in replication-associated DSB repair, as observed <em>in vitro</em>.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"153 ","pages":"Article 103889"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004361","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

Innate immune sensing and signaling: Co-opted for genome surveillance? Implications for tumorigenesis 先天免疫感知和信号传导：基因组监测的增选？对肿瘤发生的影响

IF 2.7 3区生物学

DNA Repair Pub Date : 2025-09-01 DOI: 10.1016/j.dnarep.2025.103890

Hexiao Wang, John H.J. Petrini

{"title":"Innate immune sensing and signaling: Co-opted for genome surveillance? Implications for tumorigenesis","authors":"Hexiao Wang, John H.J. Petrini","doi":"10.1016/j.dnarep.2025.103890","DOIUrl":"10.1016/j.dnarep.2025.103890","url":null,"abstract":"<div><div>Innate immune signaling is traditionally associated with the response to pathogenic infection. However, emerging evidence suggests that nuclear innate immune sensors and their downstream pathways may also serve as a critical mechanism for genome surveillance. This review explores a model in which DNA sensors such as mouse IFI204 and IFI205 (IFI16 in humans) localize to replication forks, where they detect endogenous aberrant DNA structures and initiate an interferon-stimulated gene (ISG) transcriptional program. A key output of this transcriptional program is ISG15, which we find conjugated to fork-associated proteins and facilitates recruitment of the replication fork protection complex, thereby stabilizing replication forks under physiological conditions. We discuss how nuclear innate immune sensors mediate replication stress sensing and examine the broad consequences of downstream ISG transcription across diverse contexts—including its impact on genome stability and its dual roles in modulating tumor cell behavior and the tumor microenvironment. These findings suggest that the innate immune system, through its nuclear DNA sensing arm, may be evolutionarily co-opted for genome surveillance and may influence tumor initiation and therapy resistance. Understanding how innate immune signaling intersects with replication stress could offer mechanistic insights into tumor development and reveal novel therapeutic targets.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"153 ","pages":"Article 103890"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026420","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

DNA damage response inhibitors in cancer therapy: Mechanisms, clinical development, and combination strategies DNA损伤反应抑制剂在癌症治疗中的应用：机制、临床发展和联合策略

IF 2.7 3区生物学

DNA Repair Pub Date : 2025-08-21 DOI: 10.1016/j.dnarep.2025.103887

Seon-gyeong Lee , Jinwoo Kim , Euihwan Jeong , Kyungjae Myung

{"title":"DNA damage response inhibitors in cancer therapy: Mechanisms, clinical development, and combination strategies","authors":"Seon-gyeong Lee , Jinwoo Kim , Euihwan Jeong , Kyungjae Myung","doi":"10.1016/j.dnarep.2025.103887","DOIUrl":"10.1016/j.dnarep.2025.103887","url":null,"abstract":"<div><div>Impaired genomic stability is a hallmark of many cancers, with the DNA damage response (DDR) mechanisms serving as critical safeguards for maintaining genomic integrity. These intricate DDR networks, encompassing various DNA repair and damage checkpoint pathways, are essential for regulating the cell cycle, immune responses, and apoptosis. Notably, defects in DDR pathways, particularly those involving BRCA1/2 mutations, present exploitable vulnerabilities for targeted therapies such as PARP inhibitors (PARPi). This review explores the mechanisms by which PARPi function as cancer therapies, focusing on their ability to inhibit DNA repair processes and induce tumor cell death. It also examines the current landscape of PARPi clinical trials and their application across various cancer types. In addition, we discuss emerging DDR inhibitors, including CHK1/2, ATR, ATM, RAD51, APE1, and WEE1, many of which act by inhibiting DNA repair and damage checkpoints. These inhibitors selectively target malignant cells that are deficient in checkpoint function, thereby inducing replication stress and mitotic catastrophe. While DDR inhibitors hold great potential as standalone therapies or in combination with chemotherapy, immunotherapy, and radiation, challenges persist, including overlapping toxicities and damage to healthy tissues. This review aims to illuminate the rapidly advancing field of DDR-based targeted cancer therapies, emphasizing their potential to revolutionize treatment approaches and improve patient outcomes.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"153 ","pages":"Article 103887"},"PeriodicalIF":2.7,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895334","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

Insight into meiotic DNA end resection: Mechanisms and regulation 洞察减数分裂DNA末端切除：机制和调控

IF 2.7 3区生物学

DNA Repair Pub Date : 2025-08-15 DOI: 10.1016/j.dnarep.2025.103886

Soonjoung Kim , Hasan F. Alnaser , Scott Keeney , Hajime Murakami

{"title":"Insight into meiotic DNA end resection: Mechanisms and regulation","authors":"Soonjoung Kim , Hasan F. Alnaser , Scott Keeney , Hajime Murakami","doi":"10.1016/j.dnarep.2025.103886","DOIUrl":"10.1016/j.dnarep.2025.103886","url":null,"abstract":"<div><div>Meiosis generates reproductive cells with a reduced genome complement, with most species using homologous recombination to promote accurate meiotic chromosome segregation and to generate genetic diversity among offspring. A critical step in homologous recombination is DNA end resection, in which DNA double-strand breaks (DSBs) are processed by nucleases to yield the 3′ single-stranded DNA (ssDNA) needed for homology search and strand invasion. DSB resection in nonmeiotic contexts has been extensively studied, but meiotic resection is less well understood. We provide here a review of studies elucidating the mechanism and regulation of resection during meiosis, covering similarities and differences from resection in mitotically dividing cells. The nucleases that carry out resection are discussed, along with resection-modulating factors such as DNA damage signaling and chromatin structure. We focus on the budding yeast <em>Saccharomyces cerevisiae</em> and on mouse, for which the most information is currently available, but also describe studies in other species that point to evolutionary conservation or divergence in this key process needed for genome integrity in the germline.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"153 ","pages":"Article 103886"},"PeriodicalIF":2.7,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890231","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

DNA Repair最新文献