The kleisin subunit of cohesin dictates damage-induced cohesion
The kleisin subunit of cohesin dictates damage-induced cohesion
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DOI：
10.1016/j.molcel.2008.06.005
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发表时间：
2008-07-11
期刊：
影响因子：
16
通讯作者：
Koshland, Douglas
中科院分区：
文献类型：
--
作者：
Heidinger-Pauli, Jill M.;Unal, Elcin;Koshland, Douglas
凝聚素是一种介导姐妹染色单体凝聚的蛋白质复合物，是染色体分离和双链断裂修复所必需的。凝聚力的产生通常限于S相。然而，在G2/M中，DSB激活DSB附近和全基因组范围内的内聚生成。在这里，使用芽殖酵母，我们表明，DSB诱导的凝聚力发生时，凝聚素含有Kleisin亚基，Mcd 1（Scc 1），但不是当Mcd 1被其减数分裂亚型，Rec 8取代。我们利用这种分歧，以证明丝氨酸83 Mcd 1和Chk 1激酶是DSB诱导的凝聚力的关键决定因素。我们建议，在G2/M的DSB激活Mec 1（ATR），这反过来又刺激Chk 1依赖的磷酸化Mcd 1在丝氨酸83。丝氨酸83磷酸化促进染色质结合的粘附素变得有粘性。
Cohesin, the protein complex that mediates sister chromatid cohesion, is required for faithful chromosome segregation and efficient repair of double-strand breaks (DSBs). Cohesion generation is normally restricted to S phase. However, in G2/M, a DSB activates cohesion generation near the DSB and genome-wide. Here, using budding yeast, we show that DSB-induced cohesion occurs when cohesin contains the kleisin subunit, Mcd1 (Scc1), but not when Mcd1 is replaced by its meiotic isoform, Rec8. We exploit this divergence to demonstrate that serine 83 of Mcd1 and the Chk1 kinase are critical determinants for DSB-induced cohesion. We propose that a DSB in G2/M activates Mec1 (ATR), which in turn stimulates Chk1-dependent phosphorylation of Mcd1 at serine 83. Serine 83 phosphorylation promotes chromatin-bound cohesin to become cohesive.