Most proteins involved in the DNA double-strand break response (DSBR) accumulate at the damage sites, where they perform functions related to damage signaling, chromatin remodeling and repair. Over the last two decades, studying the accumulation of many DSBR proteins provided information about their functionality and underlying mechanisms of action. However, comparison and systemic interpretation of these data is challenging due to their scattered nature and differing experimental approaches. Here, we extracted, analyzed and compared the available results describing accumulation of 79 DSBR proteins at sites of DNA damage, which can be further explored using Cumulus (http://www.dna-repair.live/cumulus/)—the accompanying interactive online application. Despite large inter-study variability, our analysis revealed that the accumulation of most proteins starts immediately after damage induction, occurs in parallel and peaks within 15–20 min. Various DSBR pathways are characterized by distinct accumulation kinetics with major non-homologous end joining proteins being generally faster than those involved in homologous recombination, and signaling and chromatin remodeling factors accumulating with varying speeds. Our meta-analysis provides, for the first time, comprehensive overview of the temporal organization of the DSBR in mammalian cells and could serve as a reference for future mechanistic studies of this complex process.

中文翻译：

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DNA 双链断裂反应动力学的 Meta 分析


大多数参与 DNA 双链断裂反应 (DSBR) 的蛋白质都会在损伤位点积累，在那里它们执行与损伤信号传导、染色质重塑和修复相关的功能。在过去的二十年中，对许多 DSBR 蛋白积累的研究提供了有关其功能和潜在作用机制的信息。然而，由于这些数据的分散性和不同的实验方法，对这些数据的比较和系统解释具有挑战性。在这里，我们提取、分析和比较了描述 79 个 DSBR 蛋白在 DNA 损伤位点积累的可用结果，可以使用Cumulus (http://www.dna-repair.live/cumulus/)（随附的交互式工具）进一步探索这些结果。在线申请。尽管研究间存在很大差异，但我们的分析表明，大多数蛋白质的积累在损伤诱导后立即开始，并行发生，并在 15-20 分钟内达到峰值。各种 DSBR 途径的特点是具有不同的积累动力学，主要的非同源末端连接蛋白通常比参与同源重组的蛋白更快，并且信号传导和染色质重塑因子以不同的速度积累。我们的荟萃分析首次提供了哺乳动物细胞中 DSBR 时间组织的全面概述，可以作为未来这一复杂过程的机制研究的参考。