{"title":"The RNA tether model for human chromosomal translocation fragile zones","authors":"Di Liu , Chih-Lin Hsieh , Michael R. Lieber","doi":"10.1016/j.tibs.2024.02.003","DOIUrl":null,"url":null,"abstract":"<div><p>One of the two chromosomal breakage events in recurring translocations in B cell neoplasms is often due to the recombination-activating gene complex (RAG complex) releasing DNA ends before end joining. The other break occurs in a fragile zone of 20–600 bp in a non-antigen receptor gene locus, with a more complex and intriguing set of mechanistic factors underlying such narrow fragile zones. These factors include activation-induced deaminase (AID), which acts only at regions of single-stranded DNA (ssDNA). Recent work leads to a model involving the tethering of AID to the nascent RNA as it emerges from the RNA polymerase. This mechanism may have relevance in class switch recombination (CSR) and somatic hypermutation (SHM), as well as broader relevance for other DNA enzymes.</p></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 5","pages":"Pages 391-400"},"PeriodicalIF":11.6000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in Biochemical Sciences","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0968000424000392","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
One of the two chromosomal breakage events in recurring translocations in B cell neoplasms is often due to the recombination-activating gene complex (RAG complex) releasing DNA ends before end joining. The other break occurs in a fragile zone of 20–600 bp in a non-antigen receptor gene locus, with a more complex and intriguing set of mechanistic factors underlying such narrow fragile zones. These factors include activation-induced deaminase (AID), which acts only at regions of single-stranded DNA (ssDNA). Recent work leads to a model involving the tethering of AID to the nascent RNA as it emerges from the RNA polymerase. This mechanism may have relevance in class switch recombination (CSR) and somatic hypermutation (SHM), as well as broader relevance for other DNA enzymes.
在 B 细胞瘤反复发生的易位中，有两种染色体断裂现象，其中一种往往是由于重组激活基因复合物（RAG 复合物）在末端连接之前释放了 DNA 末端。另一种断裂发生在非抗原受体基因位点上 20-600 bp 的脆弱区内，这种狭窄的脆弱区有一系列更复杂、更耐人寻味的机理因素。这些因素包括活化诱导脱氨酶（AID），它只作用于单链 DNA（ssDNA）区域。最近的研究提出了一个模型，涉及 AID 在新生 RNA 从 RNA 聚合酶中产生时与新生 RNA 的系链。这种机制可能与类开关重组（CSR）和体细胞超突变（SHM）有关，也与其他 DNA 酶有关。
期刊介绍：
For over 40 years, Trends in Biochemical Sciences (TIBS) has been a leading publication keeping readers informed about recent advances in all areas of biochemistry and molecular biology. Through monthly, peer-reviewed issues, TIBS covers a wide range of topics, from traditional subjects like protein structure and function to emerging areas in signaling and metabolism. Articles are curated by the Editor and authored by top researchers in their fields, with a focus on moving beyond simple literature summaries to providing novel insights and perspectives. Each issue primarily features concise and timely Reviews and Opinions, supplemented by shorter articles including Spotlights, Forums, and Technology of the Month, as well as impactful pieces like Science & Society and Scientific Life articles.
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