DNA Repair最新文献_第7页

Cytosolic DNA and intracellular Ca2+: Maintaining genome stability during replication stress 胞质DNA和细胞内Ca2+：在复制胁迫下维持基因组的稳定性

IF 2.7 3区生物学

DNA Repair Pub Date : 2025-08-01 Epub Date: 2025-07-28 DOI: 10.1016/j.dnarep.2025.103877

Shan Li , Hsiang-Ting Lu , Zhongsheng You

{"title":"Cytosolic DNA and intracellular Ca2+: Maintaining genome stability during replication stress","authors":"Shan Li , Hsiang-Ting Lu , Zhongsheng You","doi":"10.1016/j.dnarep.2025.103877","DOIUrl":"10.1016/j.dnarep.2025.103877","url":null,"abstract":"<div><div>Maintaining genome stability during DNA replication is a critical cellular challenge. Various surveillance and repair mechanisms have evolved to cope with replication stress, which can be caused by environmental insults, metabolic byproducts, complex DNA structures in the genome, and replication-transcription conflicts. This perspective highlights a newly identified cytosolic DNA/Ca<sup>2+</sup>-dependent signaling pathway that plays a crucial role in protecting stalled replication forks. The pathway involves cytosolic DNA generation and its sensing by the cGAS-cGAMP-STING axis, TRPV2-mediated Ca<sup>2+</sup> release from the ER, and activation of a CaMKK2-AMPK protein phosphorylation cascade that suppresses the EXO1 nuclease, thereby preventing aberrant fork processing and preserving chromosomal integrity. Separate from the ATR/Chk1 checkpoint, this cytoDNA/Ca<sup>2+</sup>-dependent pathway represents a non-redundant mechanism for genome maintenance, with potentially important implications for cancer formation and its treatment. Moreover, the intersection of this pathway with other signaling networks also enables coordinated regulation of genome maintenance, immune response, autophagy, and cellular senescence.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"152 ","pages":"Article 103877"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763874","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

Unveiling cGAS mechanisms: Insights into DNA damage and immune sensing in cancer 揭示cGAS机制：对癌症中DNA损伤和免疫感知的见解

IF 3 3区生物学

DNA Repair Pub Date : 2025-08-01 Epub Date: 2025-07-09 DOI: 10.1016/j.dnarep.2025.103868

Min-Guk Cho , Gaorav P. Gupta

{"title":"Unveiling cGAS mechanisms: Insights into DNA damage and immune sensing in cancer","authors":"Min-Guk Cho , Gaorav P. Gupta","doi":"10.1016/j.dnarep.2025.103868","DOIUrl":"10.1016/j.dnarep.2025.103868","url":null,"abstract":"<div><div>The innate immune sensing system plays a critical role in recognizing and responding to DNA damage, which is a key factor in cancer development and progression. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, in particular, detects cytosolic double-stranded DNA (dsDNA) and activates the innate immune response. Recent studies have shown that cGAS is sequestered on chromatin by binding to the acidic patch (AP) regions of histones. Upon DNA damage, its ability to bind to chromatin-associated dsDNA fragments requires the DNA damage sensor MRE11. Upon its activation, cGAS triggers an innate immune response that can suppress tumorigenesis. However, the context-specific factors that govern whether cGAS engagement leads to effective STING pathway activation remain incompletely defined, particularly in relation to chromatin context, micronuclear integrity, and post-translational modifications. In this review, we explore the dynamic interplay between DNA damage responses and innate immune signaling through the cGAS-STING axis, with a focus on recent mechanistic advances. We further examine how cancers evade or co-opt this pathway and highlight therapeutic opportunities to exploit cGAS-STING signaling for cancer treatment.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"152 ","pages":"Article 103868"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655747","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

Multiple functions of PARP1 in the repair of DNA double strand breaks PARP1在DNA双链断裂修复中的多重功能

IF 3 3区生物学

DNA Repair Pub Date : 2025-08-01 Epub Date: 2025-07-21 DOI: 10.1016/j.dnarep.2025.103873

Raquel Ortega , Benjamin G. Bitler , Nausica Arnoult

{"title":"Multiple functions of PARP1 in the repair of DNA double strand breaks","authors":"Raquel Ortega , Benjamin G. Bitler , Nausica Arnoult","doi":"10.1016/j.dnarep.2025.103873","DOIUrl":"10.1016/j.dnarep.2025.103873","url":null,"abstract":"<div><div>Poly(ADP-ribose) polymerase 1 (PARP1) is one of the most abundant nuclear proteins in human cells and plays critical roles in numerous cellular processes, including the response to DNA damage. PARP1 is activated by and rapidly localizes to both single- and double-strand breaks, where it catalyzes the addition of poly(ADP-ribose) chains onto itself and other chromatin- or repair-associated proteins. While the role of PARP in single-strand break repair is established, its functions at double-strand breaks (DSBs) are more complex, as it can promote or inhibit various steps in the multiple pathways that repair DSBs. In this review, we examine the DSB repair contributions of PARP1, as well as those of PARP2 and PARP3, which are also activated upon damage. We discuss their influence on chromatin regulation at break sites, their role in repair pathway selection, and finally, the regulation of repair mechanisms, including homologous recombination, non-homologous end-joining, and microhomology-mediated end-joining. Understanding these diverse and sometimes opposing roles is especially important in light of the clinical use of PARP inhibitors in cancers deficient in homologous recombination repair.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"152 ","pages":"Article 103873"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695153","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

Altered pathways in Cockayne syndrome: Involvement of MAPK, PI3K-Akt, extracellular matrix, inflammation, and neuronal signaling Cockayne综合征的通路改变：MAPK、PI3K-Akt、细胞外基质、炎症和神经元信号的参与

IF 3 3区生物学

DNA Repair Pub Date : 2025-08-01 Epub Date: 2025-06-22 DOI: 10.1016/j.dnarep.2025.103861

Gustavo Satoru Kajitani , Marina Andrade Tomaz , Giovana da Silva Leandro , Carolina Quayle , Lorrana Cachuite Mendes Rocha , Tiago Antonio de Souza , Leandro Márcio Moreira , Izinara Rosse , Carlos Frederico Martins Menck , Camila Carrião Machado Garcia

{"title":"Altered pathways in Cockayne syndrome: Involvement of MAPK, PI3K-Akt, extracellular matrix, inflammation, and neuronal signaling","authors":"Gustavo Satoru Kajitani , Marina Andrade Tomaz , Giovana da Silva Leandro , Carolina Quayle , Lorrana Cachuite Mendes Rocha , Tiago Antonio de Souza , Leandro Márcio Moreira , Izinara Rosse , Carlos Frederico Martins Menck , Camila Carrião Machado Garcia","doi":"10.1016/j.dnarep.2025.103861","DOIUrl":"10.1016/j.dnarep.2025.103861","url":null,"abstract":"<div><div>Cockayne syndrome (CS) is a disorder characterized by neurodegeneration and a segmental progeroid phenotype, resulting from mutations in <em>ERCC8/CSA</em> or <em>ERCC6/CSB</em> genes. These genes encode proteins essential for the DNA repair pathway known as transcription-coupled nucleotide excision repair (TC-NER). To further investigate the biological pathways associated with this phenotype, we analyzed transcriptome datasets specific to CS. We conducted RNA-seq on the Csa<sup>-/-</sup> mouse model at three different age timepoints, and re-analyzed 8 microarray- or RNA-seq based CS transcriptomes present in Gene Expression Omnibus that contained appropriate isogenic controls. We identified differentially expressed genes in each dataset, which were subsequently used for pathway enrichment analysis. Our findings revealed that gene expression of <em>CCL2</em> and <em>VCAN</em> was altered in the majority of the CS transcriptomes analyzed. Over-representation enrichment analyses of human CS transcriptomes revealed significant changes in genes related to the MAPK, ERK1/2, PI3K-Akt pathways, alongside pathways related to neuronal processes and extracellular matrix metabolism. Additionally, gene-set enrichment analysis of nervous tissue CS datasets highlighted terms related to inflammation and synapse biology. These pathways and processes may contribute to the neurological dysfunction and overall phenotype of CS, presenting promising avenues for future research into the etiology and potential treatments for this aging-related disorder.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"152 ","pages":"Article 103861"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480710","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

Using the safety scissors: DNA resection regulation at DNA double-strand breaks and telomeres 使用安全剪刀：DNA双链断裂和端粒的DNA切除调控

IF 3 3区生物学

DNA Repair Pub Date : 2025-08-01 Epub Date: 2025-07-23 DOI: 10.1016/j.dnarep.2025.103876

Michael M. Soniat , Logan R. Myler

引用次数: 0

DNA topoisomerase IIß inhibition blocks DNA end resection and synergizes with PARPi in BRCA1-deficient models 在brca1缺陷模型中，DNA拓扑异构酶isß抑制阻断DNA末端切除并与PARPi协同作用

IF 3 3区生物学

DNA Repair Pub Date : 2025-08-01 Epub Date: 2025-06-27 DOI: 10.1016/j.dnarep.2025.103866

Rosa Camarillo , Rosario Prados-Carvajal , Andrés Cruz-García , Guillermo Rodríguez-Real , Andrea Herencia-Ropero , Violeta Serra , Sonia Jimeno , Pablo Huertas

{"title":"DNA topoisomerase IIß inhibition blocks DNA end resection and synergizes with PARPi in BRCA1-deficient models","authors":"Rosa Camarillo , Rosario Prados-Carvajal , Andrés Cruz-García , Guillermo Rodríguez-Real , Andrea Herencia-Ropero , Violeta Serra , Sonia Jimeno , Pablo Huertas","doi":"10.1016/j.dnarep.2025.103866","DOIUrl":"10.1016/j.dnarep.2025.103866","url":null,"abstract":"<div><div>DNA end resection is a critical step that governs how a broken chromosome will be repaired. As such, it is heavily regulated by multiple cellular signals and processes. Alterations in the regulation of DNA end resection have consequences for cell survival upon exposure to cytotoxic agents, including those used during cancer chemotherapy. Here, we identified several small molecules that affect the process of DNA end resection. Among them, we focus on determining the mode of action of merbarone, a DNA topoisomerase II inhibitor. We uncover a role of the topoisomerase IIβ isoform in the full processing of DNA breaks. Moreover, we show that the effect of merbarone is affected by the formation of G4 quadruplexes and that <em>BRCA1</em>-deficient cancer cells are sensitive to merbarone. Strikingly, this sensitivity can be partially suppressed in cell lines expressing hypomorphic versions of BRCA1 lacking exon 11, a hypomorph that has been linked to PARPi-resistance. Using cellular models, we show that PARPi- and merbarone-resistant BRCA1 exon 11 mutant cells, but not wildtype BRCA1 cells, are sensitive to the combination of both drugs. Finally, we show that combination of merbarone and the PARPi olaparib has a mild antitumor effect in a PARPi-resistant PDX model bearing a BRCA1 exon 11 mutation.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"152 ","pages":"Article 103866"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517280","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

Treatment of human cells with the anti-cancer drug cisplatin results in the caspase-dependent release of adduct-containing cell-free DNA 用抗癌药物顺铂治疗人类细胞导致caspase依赖性释放含加合物的无细胞DNA

IF 3 3区生物学

DNA Repair Pub Date : 2025-07-01 Epub Date: 2025-06-12 DOI: 10.1016/j.dnarep.2025.103855

Sri Meghana Yerrapragada , Aleena Alex , Sheera Adar , Michael G. Kemp , M. Alexandra Carpenter

{"title":"Treatment of human cells with the anti-cancer drug cisplatin results in the caspase-dependent release of adduct-containing cell-free DNA","authors":"Sri Meghana Yerrapragada , Aleena Alex , Sheera Adar , Michael G. Kemp , M. Alexandra Carpenter","doi":"10.1016/j.dnarep.2025.103855","DOIUrl":"10.1016/j.dnarep.2025.103855","url":null,"abstract":"<div><div>Cell-free DNA (cfDNA) found in biofluids is increasingly being used in the diagnosis and treatment of a variety of disease states, including cancer. Though DNA is known to be susceptible to damage by many different chemotherapeutic compounds and genotoxic agents, the fact that cfDNA may be damaged and contain DNA adducts associated with specific exposures has not previously been considered to any significant extent. Here, using differential centrifugation of culture medium from cells treated with the anti-cancer drug cisplatin, we show that DNA containing cisplatin adducts is readily detectable in the extracellular milieu and is enriched in fractions known to contain small extracellular vesicles and cfDNA. However, our data indicates that this damaged cfDNA is non-vesicular in nature and likely represents fragments of chromatin. Dose and time course experiments suggest that the release of cfDNA containing cisplatin-DNA adducts is correlated with the activation of apoptotic signaling. Indeed, the generation of cisplatin-damaged cfDNA is exacerbated by the loss of nucleotide excision repair and is abrogated by caspase inhibition. Finally, we show that native cisplatin-damaged cfDNA, but not purified, protein-free cfDNA, can be taken up by cells by phagocytosis to result in the presence of cisplatin-DNA adduct-containing DNA in non-cisplatin-treated cells. These results indicate that tumors from patients undergoing cisplatin-based chemotherapy may shed damaged cfDNA that could have additional biological effects in bystander cells, which could both impact chemotherapeutic responses and lead to improved treatments and diagnostic tools for monitoring therapeutic efficacy.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"151 ","pages":"Article 103855"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263756","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

Checkpoint activation and recovery: regulation of the 9–1–1 axis by the PP2A phosphatase 检查点激活和恢复：PP2A磷酸酶对9-1-1轴的调控

IF 3 3区生物学

DNA Repair Pub Date : 2025-07-01 Epub Date: 2025-06-06 DOI: 10.1016/j.dnarep.2025.103854

Erika Casari, Renata Tisi, Maria Pia Longhese

{"title":"Checkpoint activation and recovery: regulation of the 9–1–1 axis by the PP2A phosphatase","authors":"Erika Casari, Renata Tisi, Maria Pia Longhese","doi":"10.1016/j.dnarep.2025.103854","DOIUrl":"10.1016/j.dnarep.2025.103854","url":null,"abstract":"<div><div>Genome integrity is continuously monitored by elaborate cellular networks, collectively referred to as the DNA damage response (DDR), which detect DNA lesions and transmit the information to downstream targets, thereby coordinating a broad range of biological processes. A crucial signal in this response is the generation of single-stranded DNA that, once coated by replication protein A (RPA), serves as a platform for recruiting the apical checkpoint kinase Mec1/ATR. Full activation of Mec1/ATR also requires the 9–1–1 complex, which provides a docking site for additional checkpoint mediators, such as Dpb11/TOPBP1 and Rad9/53BP1. These mediators are important for transducing the checkpoint signal from Mec1/ATR to the effector kinase Rad53/CHK2. The checkpoint signal transduction cascade is tightly regulated by phosphorylation events, which can be counteracted by phosphatases to ensure timely checkpoint inactivation once DNA repair is complete. In this review, we examine the mechanistic aspects of Mec1/ATR activation, with a particular focus on the 9–1–1 checkpoint axis in <em>Saccharomyces cerevisiae</em>. We discuss how phosphorylation and dephosphorylation dynamically regulate the checkpoint pathway, allowing cells to efficiently respond to genotoxic stress while ensuring a timely return to normal cell-cycle progression.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"151 ","pages":"Article 103854"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241103","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

Initiation of base excision repair is modulated by nucleosome occupancy modifying sequences 碱基切除修复的启动是由核小体占用修饰序列调节的

IF 3 3区生物学

DNA Repair Pub Date : 2025-06-01 Epub Date: 2025-05-23 DOI: 10.1016/j.dnarep.2025.103852

Giovannia M. Barbosa, Sarah Delaney

{"title":"Initiation of base excision repair is modulated by nucleosome occupancy modifying sequences","authors":"Giovannia M. Barbosa, Sarah Delaney","doi":"10.1016/j.dnarep.2025.103852","DOIUrl":"10.1016/j.dnarep.2025.103852","url":null,"abstract":"<div><div>Nucleosome occupancy varies across the genome and plays a critical role in modulating DNA accessibility. While the effect of occupancy on gene expression has been studied, its influence on DNA repair, particularly base excision repair (BER), remains unexplored. In this work, we investigate the relationship between nucleosome occupancy and the initiation of BER by reconstituting nucleosome core particles (NCPs) using four DNA sequences known to modulate nucleosome occupancy <em>in vivo</em>. The results demonstrate that histone-DNA interactions differ significantly among these sequences. Moreover, uracil DNA glycosylase (UDG) activity is limited to solution-accessible uracil (U) lesion sites on NCPs containing the high occupancy sequences M4 and SB. In contrast, UDG displays high activity on NCPs containing the low occupancy sequences M2 and M3, even at less solution accessible lesion sites. In fact, for NCPs containing the sequence with the lowest occupancy, M2, UDG exhibits high activity regardless of the U lesion position. However, this high level of activity regardless of lesion position was not observed for thymine DNA glycosylase (TDG) and single-stranded monofunctional uracil DNA glycosylase 1 (SMUG1). Instead, the activity of TDG was dictated by the sequence flanking the U with a preference for 5′-UpG-3′ and 5′-UpA-3′ sequences, consistent with the role of TDG in epigenetic regulation. SMUG1 activity is high at many U sites but is severely hindered in the dyad region. These results highlight the interplay between nucleosome occupancy and BER, offering new insights into the dynamics of chromatin and DNA repair.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"150 ","pages":"Article 103852"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177901","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

Development and characterization of a novel NEIL1 nanobody 一种新型NEIL1纳米体的研制与表征

IF 3 3区生物学

DNA Repair Pub Date : 2025-06-01 Epub Date: 2025-05-22 DOI: 10.1016/j.dnarep.2025.103849

Marlo K. Thompson , Mark H. Eggers , Danielle Flores , Israel Valenzuela , Zhengrong Yang , Joel F. Andrews , Tom Johnsten , Aishwarya Prakash

{"title":"Development and characterization of a novel NEIL1 nanobody","authors":"Marlo K. Thompson , Mark H. Eggers , Danielle Flores , Israel Valenzuela , Zhengrong Yang , Joel F. Andrews , Tom Johnsten , Aishwarya Prakash","doi":"10.1016/j.dnarep.2025.103849","DOIUrl":"10.1016/j.dnarep.2025.103849","url":null,"abstract":"<div><div>Nei endonuclease VIII-like 1 (NEIL1) is a bifunctional human DNA glycosylase that catalyzes the first step of the base excision repair (BER) pathway by recognizing and excising oxidized bases, including thymine glycol and the further oxidation products of 7,8-dihydro-8-oxoguanine (8-oxoG), spiroiminodihydantoin, and guanidinohydantoin. Despite its critical role in maintaining genome stability, NEIL1 is expressed at relatively low endogenous cellular levels compared to other BER proteins such as OGG1, Polβ, and APE1. As a result, most cellular studies have relied on overexpression systems. Additionally, progress in studying NEIL1 has been hindered by the inconsistent availability and continuity of specific commercially available antibodies. To address this challenge, we developed single-domain nanobodies (VHHs) targeting NEIL1. A yeast 2 hybrid (Y2H) screen identified ten VHH hits with the top candidate, henceforth called A5, emerging multiple times. Here, we characterize the binding properties of A5 using a combination of biochemical and molecular techniques. Differential scanning fluorimetry and glycosylase activity assays indicate that recombinant A5 specifically stabilizes recombinantly expressed NEIL1, while not interfering with its glycosylase activity. Moreover, our data suggest that A5 preferentially binds to NEIL1’s N-terminal glycosylase domain rather than its C-terminal flexible tail, which is known to mediate protein-protein interactions. In live-cell imaging studies, an A5-mCherry chromobody colocalizes with NEIL1-GFP and is recruited to sites of laser-induced DNA damage, suggesting its potential as a molecular tool for visualizing NEIL1 dynamics. These findings establish A5 as a valuable probe for studying NEIL1 function and opens new avenues for exploring its role in DNA repair.</div></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"150 ","pages":"Article 103849"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169572","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