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端粒间重复序列相关的 DNA 断裂。

Interstitial telomeric repeats-associated DNA breaks.

机构信息

a Chemistry Department , M.V. Lomonosov Moscow State University , Moscow , Russia.

b A.N. Belozersky Institute of Physico-chemical Biology , M.V. Lomonosov Moscow State University , Moscow , Russia.

出版信息

Nucleus. 2017 Nov 2;8(6):641-653. doi: 10.1080/19491034.2017.1356501. Epub 2017 Sep 15.

Abstract

During a cell's lifespan, DNA break formation is a common event, associated with many processes, from replication to apoptosis. Most of DNA breaks are readily repaired, but some are meant to persist in time, such as the chromosome ends, protected by telomeres. Besides them, eukaryotic genomes comprise shorter stretches of interstitial telomeric repeats. We assumed that the latter may also be associated with the formation of DNA breaks meant to persist in time. In zebrafish and mouse embryos, cells containing numerous breakage foci were identified. These breaks were not associated with apoptosis or replication, nor did they seem to activate DNA damage response machinery. Unlike short-living, accidental sparse breaks, the ones we found seem to be closely associated, forming discrete break foci. A PCR-based method was developed, allowing specific amplification of DNA regions located between inverted telomeric repeats associated with breaks. The cloning and sequencing of such DNA fragments were found to denote some specificity in their distribution for different tissue types and development stages.

摘要

在细胞的生命周期中,DNA 断裂的形成是一种常见事件,与许多过程相关,包括复制到细胞凋亡。大多数 DNA 断裂很容易被修复,但有些则是为了持久存在,例如染色体末端,由端粒保护。除此之外,真核基因组还包含较短的染色体间端粒重复序列。我们假设后者也可能与旨在持久存在的 DNA 断裂的形成有关。在斑马鱼和小鼠胚胎中,鉴定出含有大量断裂焦点的细胞。这些断裂与细胞凋亡或复制无关,也似乎没有激活 DNA 损伤反应机制。与短暂的、偶然的稀疏断裂不同,我们发现的这些断裂似乎密切相关,形成离散的断裂焦点。开发了一种基于 PCR 的方法,允许对与断裂相关的倒置端粒重复序列之间的 DNA 区域进行特异性扩增。对这些 DNA 片段的克隆和测序发现,它们在不同的组织类型和发育阶段的分布具有一定的特异性。

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