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首页> 外文期刊>Molecular and Cellular Biology >Distinct Functions of Human Cohesin-SA1 and Cohesin-SA2 in Double-Strand Break Repair
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Distinct Functions of Human Cohesin-SA1 and Cohesin-SA2 in Double-Strand Break Repair

机译：人Cohesin-SA1和Cohesin-SA2在双链断裂修复中的不同功能

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Cohesin is an essential multiprotein complex that mediates sister chromatid cohesion critical for proper segregation of chromosomes during cell division. Cohesin is also involved in DNA double-strand break (DSB) repair. In mammalian cells, cohesin is involved in both DSB repair and the damage checkpoint response, although the relationship between these two functions is unclear. Two cohesins differing by one subunit (SA1 or SA2) are present in somatic cells, but their functional specificities with regard to DNA repair remain enigmatic. We found that cohesin-SA2 is the main complex corecruited with the cohesin-loading factor NIPBL to DNA damage sites in an S/G2-phase-specific manner. Replacing the diverged C-terminal region of SA1 with the corresponding region of SA2 confers this activity on SA1. Depletion of SA2 but not SA1 decreased sister chromatid homologous recombination repair and affected repair pathway choice, indicating that DNA repair activity is specifically associated with cohesin recruited to damage sites. In contrast, both cohesin complexes function in the intra-S checkpoint, indicating that cell cycle-specific damage site accumulation is not a prerequisite for cohesin's intra-S checkpoint function. Our findings reveal the unique ways in which cohesin-SA1 and cohesin-SA2 participate in the DNA damage response, coordinately protecting genome integrity in human cells.
机译：粘着蛋白是一种重要的多蛋白复合物，可介导染色单体的内聚，对细胞分裂过程中染色体的正确分离至关重要。粘着素还参与DNA双链断裂（DSB）修复。在哺乳动物细胞中，粘附素参与DSB修复和损伤检查点反应，尽管这两种功能之间的关系尚不清楚。体细胞中存在两种具有一个亚基（SA1或SA2）不同的粘着蛋白，但它们在DNA修复方面的功能特异性仍然令人迷惑。我们发现，cohesin-SA2是与cohesin加载因子NIPBL特异性结合的主要复合物，它以S / G 2 相的方式对DNA损伤位点起作用。用SA2的相应区域替换SA1的C末端分叉的区域可以使SA1上具有此活动。 SA2的耗竭而不是SA1的耗竭会减少姐妹染色单体同源重组修复并影响修复途径的选择，这表明DNA修复活性与募集到损伤部位的粘着蛋白特别相关。相反，两种黏着蛋白复合物均在S内检查点起作用，这表明细胞周期特异性损伤位点的积累不是黏着S内检查点功能的前提。我们的发现揭示了粘附素SA1和粘附素S​​A2参与DNA损伤反应的独特方式，从而协调地保护了人类细胞中的基因组完整性。

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