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引用次数: 0
摘要
近年来,在了解端粒替代性延长(ALT)机制的复杂细节方面取得了重大进展。对专门的 DNA 链断裂修复机制(称为断裂诱导复制)的研究,以及端粒特异性 DNA 损伤策略和蛋白质组学方法的出现,使人们能够发现协调 ALT 的同源定向 DNA 修复和 DNA 合成过程的蛋白质网络。这些网络将同源重组、DNA 模板切换、长程模板定向 DNA 合成和 DNA 链解析的介质与依赖于 SUMO 的液态凝结物形成结合起来,形成了离散的核体,端粒就在这些核体中延伸。本综述将讨论这些网络如何通过ALT机制合作介导端粒延伸的最新发现,以及它们对ALT癌细胞端粒功能和完整性的影响。
Mechanisms of Alternative Lengthening of Telomeres.
In recent years, significant advances have been made in understanding the intricate details of the mechanisms underlying alternative lengthening of telomeres (ALT). Studies of a specialized DNA strand break repair mechanism, known as break-induced replication, and the advent of telomere-specific DNA damaging strategies and proteomic methodologies to profile the ribonucleoprotein composition of telomeres enabled the discovery of networks of proteins that coordinate the stepwise homology-directed DNA repair and DNA synthesis processes of ALT. These networks couple mediators of homologous recombination, DNA template-switching, long-range template-directed DNA synthesis, and DNA strand resolution with SUMO-dependent liquid condensate formation to create discrete nuclear bodies where telomere extension occurs. This review will discuss the recent findings of how these networks may cooperate to mediate telomere extension by the ALT mechanism and their impact on telomere function and integrity in ALT cancer cells.
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.