Cohesin association to replication sites depends on rad50 and promotes fork restart.

Cohesin association to replication sites depends on rad50 and promotes fork restart.
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DOI:
10.1016/j.molcel.2012.07.004
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发表时间:
2012-10-12
期刊:
影响因子:
16
通讯作者:
Cobb, Jennifer A.
Cobb, Jennifer A.
中科院分区:
生物学1区
文献类型:
--
作者:
Tittel-Elmer, Mireille;Lengronne, Armelle;Davidson, Marta B.;Bacal, Julien;Francois, Philippe;Hohl, Marcel;Petrini, John H. J.;Pasero, Philippe;Cobb, Jennifer A.

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粘着蛋白复合体将新复制的染色单体结合在一起,并参与保持基因组完整性的多种途径。我们发现,在芽殖酵母中,粘附素被瞬时招募到活跃的复制起点,并随着叉的进展沿着DNA传播。当DNA合成受阻时,粘附素在复制位点积累,并且对于停滞的叉的恢复至关重要。复制叉处的粘附素富集不依赖于γH2A(X)的形成,这与其在DNA双链断裂(DSB)处的加载要求不同。然而,在rad50Δ突变体和缺乏Mec1和Tel 1检查点激酶的细胞中,粘着蛋白定位大大减少。有趣的是,复制位点的粘附素负载取决于Rad50的结构特征,这些结构特征对桥接姐妹染色单体很重要,包括CXXC钩结构域和卷曲螺旋延伸的长度。总之,这些数据揭示了在S期内,粘着蛋白在维持基因组完整性方面的功能。
The cohesin complex holds together newly-replicated chromatids and is involved in diverse pathways that preserve genome integrity. We show that in budding yeast, cohesin is transiently recruited to active replication origins and it spreads along DNA as forks progress. When DNA synthesis is impeded, cohesin accumulates at replication sites and is critical for the recovery of stalled forks. Cohesin enrichment at replication forks does not depend on γH2A(X) formation, which differs from its loading requirements at DNA double-strand breaks (DSBs). However, cohesin localization is largely reduced in rad50Δ mutants and cells lacking both Mec1 and Tel1 checkpoint kinases. Interestingly, cohesin loading at replication sites depends on the structural features of Rad50 that are important for bridging sister chromatids, including the CXXC hook domain and the length of the coiled-coil extensions. Together, these data reveal a function for cohesin in the maintenance of genome integrity during S phase.
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