{"title":"Transcription reprogramming and endogenous DNA damage","authors":"Lei Li","doi":"10.1016/j.dnarep.2024.103754","DOIUrl":null,"url":null,"abstract":"<div><p>Transcription reprogramming is essential to carry out a variety of cell dynamics such as differentiation and stress response. During reprogramming of transcription, a number of adverse effects occur and potentially compromise genomic stability. Formaldehyde as an obligatory byproduct is generated in the nucleus via oxidative protein demethylation at regulatory regions, leading to the formation of DNA crosslinking damage. Elevated levels of transcription activities can result in the accumulation of unscheduled R-loop. DNA strand breaks can form if processed 5-methylcytosines are exercised by DNA glycosylase during imprint reversal. When cellular differentiation involves a large number of genes undergoing transcription reprogramming, these endogenous DNA lesions and damage-prone structures may pose a significant threat to genome stability. In this review, we discuss how DNA damage is formed during cellular differentiation, cellular mechanisms for their removal, and diseases associated with transcription reprogramming.</p></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"142 ","pages":"Article 103754"},"PeriodicalIF":3.0000,"publicationDate":"2024-09-03","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/S1568786424001307","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
Abstract
Transcription reprogramming is essential to carry out a variety of cell dynamics such as differentiation and stress response. During reprogramming of transcription, a number of adverse effects occur and potentially compromise genomic stability. Formaldehyde as an obligatory byproduct is generated in the nucleus via oxidative protein demethylation at regulatory regions, leading to the formation of DNA crosslinking damage. Elevated levels of transcription activities can result in the accumulation of unscheduled R-loop. DNA strand breaks can form if processed 5-methylcytosines are exercised by DNA glycosylase during imprint reversal. When cellular differentiation involves a large number of genes undergoing transcription reprogramming, these endogenous DNA lesions and damage-prone structures may pose a significant threat to genome stability. In this review, we discuss how DNA damage is formed during cellular differentiation, cellular mechanisms for their removal, and diseases associated with transcription reprogramming.
转录重编程对分化和应激反应等多种细胞动态过程至关重要。在转录重编程过程中，会产生一些不利影响，并可能损害基因组的稳定性。甲醛作为一种必须的副产品，在细胞核中通过调节区域的氧化蛋白去甲基化作用生成，导致 DNA 交联损伤的形成。转录活动水平的升高会导致计划外 R 环的积累。在印记逆转过程中，如果处理过的 5-甲基胞嘧啶被 DNA 糖基化酶作用，就会形成 DNA 链断裂。当细胞分化涉及大量基因进行转录重编程时，这些内源性 DNA 损伤和易损伤结构可能会对基因组稳定性构成重大威胁。在本综述中，我们将讨论细胞分化过程中如何形成 DNA 损伤、清除损伤的细胞机制以及与转录重编程相关的疾病。
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.
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