IF 2.7

DNA repair Pub Date : 2025-09-29 DOI: 10.1016/j.dnarep.2025.103900

James Eduardo Lago Londero, Rayana Dos Santos Feltrin, Ana Lucia Anversa Segatto, André Passaglia Schuch

{"title":"CPD photolyase evolution supports amphibian UV-sensitivity hypothesis.","authors":"James Eduardo Lago Londero, Rayana Dos Santos Feltrin, Ana Lucia Anversa Segatto, André Passaglia Schuch","doi":"10.1016/j.dnarep.2025.103900","DOIUrl":"https://doi.org/10.1016/j.dnarep.2025.103900","url":null,"abstract":"The UV-sensitivity hypothesis for amphibian decline proposes that interspecific variation in cyclobutane pyrimidine dimer (CPD) photolyase activity determines species' UV sensitivity, which is linked to their natural history and population trends. Here, to shed light on the molecular basis of UV resistance variation, we investigated the evolutionary dynamics of CPD photolyases in amphibians focusing on regions and sites relevant to protein function. Our evolutionary analyses revealed that amino acids critical for CPD photolyase function are highly conserved and their codons have been evolving under purifying selection. Three tryptophan residues, critical for light-dependent repair and potentially for dark repair, are highly conserved in CPD photolyases across species. Nevertheless, we identified variations in functionally relevant CPD photolyase amino acids across amphibian clades, some of which are predicted to contract the active site and destabilize the protein structure. Caudata CPD photolyases contain functionally relevant variations likely linked to the high UV sensitivity of salamanders and newts. In Gymnophiona, we found relaxed purifying selection in CPD photolyase codons, as well as functionally relevant amino acid variations, likely reflecting the fossorial, dark-dwelling lifestyle of caecilians. Strikingly, most amphibian species with decreasing populations exhibit CPD photolyases with functionally relevant amino acid variations, and this pattern is even stronger for variations that disrupt protein structure. For example, two structurally disruptive, functionally relevant amino acid variations co-occur in CPD photolyases of species from the genera Bombina (Anura) and Ambystoma (Caudata), most of which exhibit declining populations. This study shows that species-specific differences in CPD photolyases underscore the UV-sensitivity hypothesis in amphibian ecology and conservation.","PeriodicalId":93982,"journal":{"name":"DNA repair","volume":"154 ","pages":"103900"},"PeriodicalIF":2.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of both SWI/SNF ATPases by BRM014 impairs homologous recombination, sensitizes cells to DNA damage and PARP inhibitors, and activates the cGAS/STING response. BRM014抑制SWI/SNF两种ATPases会损害同源重组，使细胞对DNA损伤和PARP抑制剂敏感，并激活cGAS/STING反应。

IF 2.7

DNA repair Pub Date : 2025-08-01 Epub Date: 2025-08-08 DOI: 10.1016/j.dnarep.2025.103884

Peter Alfano, Federico Rocha, Andrew Dille, Frank Kirk, Megan Kendall, Elisa Paul, Marit Lyon, Uma Ramakrishnan, Elisha Pendleton, Renier Vélez-Cruz

{"title":"Inhibition of both SWI/SNF ATPases by BRM014 impairs homologous recombination, sensitizes cells to DNA damage and PARP inhibitors, and activates the cGAS/STING response.","authors":"Peter Alfano, Federico Rocha, Andrew Dille, Frank Kirk, Megan Kendall, Elisa Paul, Marit Lyon, Uma Ramakrishnan, Elisha Pendleton, Renier Vélez-Cruz","doi":"10.1016/j.dnarep.2025.103884","DOIUrl":"10.1016/j.dnarep.2025.103884","url":null,"abstract":"SWI/SNF chromatin remodelers hydrolyze ATP to modulate chromatin accessibility and are mutated in up to 20 % of human cancers. The development of ATPase inhibitors and proteolysis targeting chimeras (PROTACs) have shown that SWI/SNF complexes can be therapeutic targets against cancers that require MYC expression for their survival (e.g., leukemias, prostate cancer, uveal melanoma). In this study we show that for cancers that do not depend on MYC expression, inhibition of both SWI/SNF ATPases by BRM014 impairs homologous recombination (HR) and sensitizes U2OS osteosarcoma cells and MDA-MB-231 triple negative breast cancer cells to chemotherapeutic agents that induce DNA double strand breaks (DSBs) and importantly, to PARP inhibitors (PARPi). BRM014 impaired DSB repair and the clearance of γH2AX foci. Moreover, BRM014 stimulated the use of non-homologous end joining (NHEJ) for DSB repair. Finally, BRM014 alone or in combination with olaparib also increased the frequency of micronuclei formation and activated the cGAS/STING response mediated by the activation of NFκB. Similar results were observed by inducing the degradation of both SWI/SNF ATPases by a PROTAC (AU-15330), which impaired the repair of DSBs, sensitized cells to DNA damage and PARPi. This study shows that inhibition or degradation of both SWI/SNF ATPases enhances the effects of chemotherapy, and activates the cGAS/STING response, which is associated with better therapeutic outcomes. This study shows that SWI/SNF chromatin remodelers are an important target to enhance the effects of chemotherapy and can affect the choice of DSB repair pathway.","PeriodicalId":93982,"journal":{"name":"DNA repair","volume":"152 ","pages":"103884"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toxoplasma gondii RAD51 recombinase is required to overcome DNA replication stress and its inactivation leads to bradyzoite differentiation. 弓形虫RAD51重组酶是克服DNA复制应激所必需的，其失活导致慢殖子分化。

IF 2.7

DNA repair Pub Date : 2025-08-01 Epub Date: 2025-08-07 DOI: 10.1016/j.dnarep.2025.103882

Ana M Saldarriaga Cartagena, Ayelén Aparicio Arias, Constanza Cristaldi, Agustina Ganuza, M Micaela Gonzalez, María M Corvi, William J Sullivan, Laura Vanagas, Sergio O Angel

{"title":"Toxoplasma gondii RAD51 recombinase is required to overcome DNA replication stress and its inactivation leads to bradyzoite differentiation.","authors":"Ana M Saldarriaga Cartagena, Ayelén Aparicio Arias, Constanza Cristaldi, Agustina Ganuza, M Micaela Gonzalez, María M Corvi, William J Sullivan, Laura Vanagas, Sergio O Angel","doi":"10.1016/j.dnarep.2025.103882","DOIUrl":"10.1016/j.dnarep.2025.103882","url":null,"abstract":"Toxoplasma gondii is an obligate intracellular parasite with a high replication rate that can lead to DNA replicative stress, in turn associated with the generation of DNA double-strand breaks (DSBs). Cells have two main pathways to repair DSBs: non-homologous end joining and homologous recombination repair (NHEJ and HRR respectively). RAD51 is the key recombinase in the HRR pathway. In this work, we achieved endogenous tagging of the RAD51 gene using the Auxin Inducible Degron (AID) system, to generate the clonal line RH RAD51HA-AID. Here we demonstrate that RAD51 is expressed in replicative tachyzoites and establishes damage foci. Auxin-induced knock-down (KD) affects the correct replication of tachyzoites which show loss of synchronization. The use of the RAD51 inhibitor B02 also affects parasite growth, with an IC50 of 4.8 µM. B02 produced alterations in tachyzoite replication and arrest in the S phase of the cell cycle. Additionally, B02 induced tachyzoite to bradyzoite differentiation showing small cyst-like structures. In conclusion, RAD51 is necessary for maintaining proper tachyzoite replication under normal growth conditions, supporting that genome instability occurs during the cell cycle. Our findings also suggest that DNA replication stress can induce bradyzoite differentiation.","PeriodicalId":93982,"journal":{"name":"DNA repair","volume":"152 ","pages":"103882"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Base excision repair in human cancer: Emerging diagnostic and therapeutic target. 人类癌症的基底切除修复：新兴的诊断和治疗靶点。

IF 2.7

DNA repair Pub Date : 2025-08-01 Epub Date: 2025-08-07 DOI: 10.1016/j.dnarep.2025.103879

Wenli Zhou, Xinming Jing, Ruyi Hang, Zheng Liu, Lin Cao, Mengxia Li

引用次数: 0

The role of rRNA in maintaining genome stability. rRNA 在维持基因组稳定性方面的作用。

IF 2.7

DNA repair Pub Date : 2024-07-01 Epub Date: 2024-05-12 DOI: 10.1016/j.dnarep.2024.103692

Peng Li, Xiaochun Yu

引用次数: 0

Biochemical analysis of H2O2-induced mutation spectra revealed that multiple damages were involved in the mutational process 对 H2O2 诱导的突变光谱进行的生化分析表明，突变过程涉及多种损伤

DNA repair Pub Date : 2023-12-01 DOI: 10.1016/j.dnarep.2023.103617

Tomohiko Sugiyama, Mahima R. Sanyal

引用次数: 0

Contents of Previous 3 Special Issues in this Series of Perspectives. 透视》系列前 3 期特刊的内容。

DNA repair Pub Date : 2023-12-01 DOI: 10.1016/j.dnarep.2023.103615

Penny Jeggo

引用次数: 0

UvrD-like helicase Hmi1 Has an ATP independent role in yeast mitochondrial DNA maintenance UvrD样解旋酶Hmi1在酵母线粒体DNA维持中具有ATP非依赖性作用

DNA repair Pub Date : 2023-10-11 DOI: 10.1016/j.dnarep.2023.103582

Sirelin Sillamaa, Vlad–Julian Piljukov, Iris Vaask, Tiina Sedman, Priit Jõers, Juhan Sedman

{"title":"UvrD-like helicase Hmi1 Has an ATP independent role in yeast mitochondrial DNA maintenance","authors":"Sirelin Sillamaa, Vlad–Julian Piljukov, Iris Vaask, Tiina Sedman, Priit Jõers, Juhan Sedman","doi":"10.1016/j.dnarep.2023.103582","DOIUrl":"https://doi.org/10.1016/j.dnarep.2023.103582","url":null,"abstract":"<div>Hmi1 is a UvrD-like DNA helicase required for the maintenance of the yeast Saccharomyces cerevisiae mitochondrial DNA (mtDNA). Deletion of the HMI1 ORF leads to the formation of respiration-deficient petite mutants, which either contain a short fragment of mtDNA arranged in tandem repeats or lack mtDNA completely. Here we characterize point mutants of the helicase designed to target the ATPase or ssDNA binding activity and show that these mutations do not separately lead to complete loss of the Hmi1 function. The mutant strains support ATP production via oxidative phosphorylation and enable us to directly analyze the impact of both activities on the stability of wild-type mtDNA in this petite-positive yeast. Our data reveal that Hmi1 mutants affecting ssDNA binding display a stronger defect in the maintenance of mtDNA compared to the mutants of ATP binding/hydrolysis. Hmi1 mutants impaired in ssDNA binding demonstrate sensitivity to UV irradiation and lower levels of Cox2 encoded by the mitochondrial genome. This suggests a complex and multifarious role for Hmi1 in mtDNA maintenance-linked transactions, some of which do not require the ATP-dependent helicase activity.</div>","PeriodicalId":93982,"journal":{"name":"DNA repair","volume":"132 ","pages":"Article 103582"},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41227818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Editorial Board 编辑委员会

DNA repair Pub Date : 2021-08-01 DOI: 10.1016/s1568-7864(21)00123-3

引用次数: 0

WITHDRAWN: Melatonin increases doxorubicin-induced apoptosis via oxidative DNA damage in oral squamous cell carcinoma 结论:褪黑激素通过氧化DNA损伤增加阿霉素诱导的口腔鳞状细胞癌细胞凋亡

DNA repair Pub Date : 2021-06-08 DOI: 10.1016/J.DNAREP.2021.103154

Shuang-xi Wang, M. Wei, Weiyu Zhu

引用次数: 0

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