The Role of Microhomology-Mediated End Joining (MMEJ) at Dysfunctional Telomeres.

IF 6.9 2区 生物学 Q1 CELL BIOLOGY Cold Spring Harbor perspectives in biology Pub Date : 2024-11-05 DOI:10.1101/cshperspect.a041687
David Billing, Agnel Sfeir
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Abstract

DNA double-strand break (DSB) repair pathways are crucial for maintaining genome stability and cell viability. However, these pathways can mistakenly recognize chromosome ends as DNA breaks, leading to adverse outcomes such as telomere fusions and malignant transformation. The shelterin complex protects telomeres from activation of DNA repair pathways by inhibiting nonhomologous end joining (NHEJ), homologous recombination (HR), and microhomology-mediated end joining (MMEJ). The focus of this paper is on MMEJ, an error-prone DSB repair pathway characterized by short insertions and deletions flanked by sequence homology. MMEJ is critical in mediating telomere fusions in cells lacking the shelterin complex and at critically short telomeres. Furthermore, studies suggest that MMEJ is the preferred pathway for repairing intratelomeric DSBs and facilitates escape from telomere crisis. Targeting MMEJ to prevent telomere fusions in hematologic malignancies is of potential therapeutic value.

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微同源物介导的端接(MMEJ)在功能障碍端粒中的作用
DNA 双链断裂(DSB)修复途径对维持基因组稳定性和细胞活力至关重要。然而,这些途径可能会错误地将染色体末端识别为DNA断裂,从而导致端粒融合和恶性转化等不良后果。保护蛋白复合物通过抑制非同源末端连接(NHEJ)、同源重组(HR)和微同源末端连接(MMEJ)来保护端粒免受DNA修复途径的激活。本文的重点是 MMEJ,这是一种容易出错的 DSB 修复途径,其特点是序列同源性侧翼的短插入和缺失。在缺乏保护蛋白复合体的细胞和极短端粒中,MMEJ 是介导端粒融合的关键。此外,研究表明MMEJ是修复端粒内DSB的首选途径,有助于摆脱端粒危机。以MMEJ为靶点防止血液恶性肿瘤中的端粒融合具有潜在的治疗价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
15.00
自引率
1.40%
发文量
56
审稿时长
3-8 weeks
期刊介绍: Cold Spring Harbor Perspectives in Biology offers a comprehensive platform in the molecular life sciences, featuring reviews that span molecular, cell, and developmental biology, genetics, neuroscience, immunology, cancer biology, and molecular pathology. This online publication provides in-depth insights into various topics, making it a valuable resource for those engaged in diverse aspects of biological research.
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