{"title":"探索影响 DNA 双链断裂修复途径选择的因素。","authors":"Daniyar Otarbayev , Kyungjae Myung","doi":"10.1016/j.dnarep.2024.103696","DOIUrl":null,"url":null,"abstract":"<div><p>DNA double-strand breaks (DSBs) represent one of the most severe threats to genomic integrity, demanding intricate repair mechanisms within eukaryotic cells. A diverse array of factors orchestrates the complex choreography of DSB signaling and repair, encompassing repair pathways, such as non-homologous end-joining, homologous recombination, and polymerase-θ-mediated end-joining. This review looks into the intricate decision-making processes guiding eukaryotic cells towards a particular repair pathway, particularly emphasizing the processing of two-ended DSBs. Furthermore, we elucidate the transformative role of Cas9, a site-specific endonuclease, in revolutionizing our comprehension of DNA DSB repair dynamics. Additionally, we explore the burgeoning potential of Cas9's remarkable ability to induce sequence-specific DSBs, offering a promising avenue for precise targeting of tumor cells. Through this comprehensive exploration, we unravel the intricate molecular mechanisms of cellular responses to DSBs, shedding light on both fundamental repair processes and cutting-edge therapeutic strategies.</p></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"140 ","pages":"Article 103696"},"PeriodicalIF":3.0000,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring factors influencing choice of DNA double-strand break repair pathways\",\"authors\":\"Daniyar Otarbayev , Kyungjae Myung\",\"doi\":\"10.1016/j.dnarep.2024.103696\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>DNA double-strand breaks (DSBs) represent one of the most severe threats to genomic integrity, demanding intricate repair mechanisms within eukaryotic cells. A diverse array of factors orchestrates the complex choreography of DSB signaling and repair, encompassing repair pathways, such as non-homologous end-joining, homologous recombination, and polymerase-θ-mediated end-joining. This review looks into the intricate decision-making processes guiding eukaryotic cells towards a particular repair pathway, particularly emphasizing the processing of two-ended DSBs. Furthermore, we elucidate the transformative role of Cas9, a site-specific endonuclease, in revolutionizing our comprehension of DNA DSB repair dynamics. Additionally, we explore the burgeoning potential of Cas9's remarkable ability to induce sequence-specific DSBs, offering a promising avenue for precise targeting of tumor cells. Through this comprehensive exploration, we unravel the intricate molecular mechanisms of cellular responses to DSBs, shedding light on both fundamental repair processes and cutting-edge therapeutic strategies.</p></div>\",\"PeriodicalId\":300,\"journal\":{\"name\":\"DNA Repair\",\"volume\":\"140 \",\"pages\":\"Article 103696\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-05-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"DNA Repair\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1568786424000727\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"DNA Repair","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1568786424000727","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
摘要
DNA双链断裂(DSB)是对基因组完整性最严重的威胁之一,需要真核细胞内复杂的修复机制。一系列不同的因素编排了DSB信号传递和修复的复杂程序,包括非同源末端连接、同源重组和聚合酶θ介导的末端连接等修复途径。这篇综述探讨了引导真核细胞走向特定修复途径的复杂决策过程,特别强调了双端DSB的处理过程。此外,我们还阐明了位点特异性内切酶 Cas9 在彻底改变我们对 DNA DSB 修复动态的理解方面所起的变革性作用。此外,我们还探讨了 Cas9 诱导序列特异性 DSB 的卓越能力所蕴含的巨大潜力,这为精确靶向肿瘤细胞提供了一条大有可为的途径。通过这种全面的探索,我们揭示了细胞对DSB反应的复杂分子机制,阐明了基本修复过程和前沿治疗策略。
Exploring factors influencing choice of DNA double-strand break repair pathways
DNA double-strand breaks (DSBs) represent one of the most severe threats to genomic integrity, demanding intricate repair mechanisms within eukaryotic cells. A diverse array of factors orchestrates the complex choreography of DSB signaling and repair, encompassing repair pathways, such as non-homologous end-joining, homologous recombination, and polymerase-θ-mediated end-joining. This review looks into the intricate decision-making processes guiding eukaryotic cells towards a particular repair pathway, particularly emphasizing the processing of two-ended DSBs. Furthermore, we elucidate the transformative role of Cas9, a site-specific endonuclease, in revolutionizing our comprehension of DNA DSB repair dynamics. Additionally, we explore the burgeoning potential of Cas9's remarkable ability to induce sequence-specific DSBs, offering a promising avenue for precise targeting of tumor cells. Through this comprehensive exploration, we unravel the intricate molecular mechanisms of cellular responses to DSBs, shedding light on both fundamental repair processes and cutting-edge therapeutic strategies.
期刊介绍:
DNA Repair provides a forum for the comprehensive coverage of DNA repair and cellular responses to DNA damage. The journal publishes original observations on genetic, cellular, biochemical, structural and molecular aspects of DNA repair, mutagenesis, cell cycle regulation, apoptosis and other biological responses in cells exposed to genomic insult, as well as their relationship to human disease.
DNA Repair publishes full-length research articles, brief reports on research, and reviews. The journal welcomes articles describing databases, methods and new technologies supporting research on DNA repair and responses to DNA damage. Letters to the Editor, hot topics and classics in DNA repair, historical reflections, book reviews and meeting reports also will be considered for publication.