The origin recognition complex functions in sister-chromatid cohesion in Saccharomyces cerevisiae
The origin recognition complex functions in sister-chromatid cohesion in Saccharomyces cerevisiae
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DOI：
10.1016/j.cell.2006.11.045
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发表时间：
2007-01-12
期刊：
影响因子：
64.5
通讯作者：
Gasser, Susan M.
中科院分区：
文献类型：
--
作者：
Shimada, Kenji;Gasser, Susan M.
高保真的染色体分离需要适当的时间建立的姐妹染色单体凝聚力介导的凝聚素复合物，并在中期到后期的过渡决议。我们已经研究了酵母菌株中的细胞周期进展，从该酵母菌株中的起点识别复合物蛋白Orc 2在复制前复合物组装后被耗尽。我们发现Orc 2缺失导致有丝分裂进程延迟，反映了DNAdamage和Mad 2-纺锤体检查点的激活。令人惊讶的是，姐妹染色单体的凝聚力受损Orc 2耗尽的细胞，虽然凝聚素亚基正确地与染色质。Orc 2在G2/M期晚期的再表达恢复了染色单体的凝聚力。最后，靶向Orc 2到一个特定的染色体位点抑制过早的姐妹染色单体分离本地温度敏感的粘蛋白突变。我们的结论是，ORG介导的途径，这是添加剂与粘连蛋白介导的配对姐妹染色单体的相互作用。
High-fidelity chromosomal segregation requires the properly timed establishment of sisterchromatid cohesion mediated by the Cohesin complex, and its resolution at the metaphaseto-anaphase transition. We have examined cell-cycle progression in a yeast strain from which the origin recognition complex protein Orc2 was depleted after the assembly of prereplication complexes. We find that Orc2 depletion causes a delay in progression through mitosis, reflecting activation of both the DNAdamage and Mad2-spindle checkpoints. Surprisingly, sister-chromatid cohesion is impaired in Orc2-depleted cells, although Cohesin subunits are properly associated with chromatin. Reexpression of Orc2 in late G2/M phase restores chromatid cohesion. Finally, the targeting of Orc2 to a specific chromosomal locus suppresses premature sister-chromatid separation locally in a temperature-sensitive cohesin mutant. We conclude that ORG mediates sisterchromatid interaction on a pathway that is additive with Cohesin-mediated pairing.