Cohesin Function in Cohesion, Condensation, and DNA Repair Is Regulated by Wpl1p via a Common Mechanism in Saccharomyces cerevisiae.
Cohesin Function in Cohesion, Condensation, and DNA Repair Is Regulated by Wpl1p via a Common Mechanism in Saccharomyces cerevisiae.
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DOI：
10.1534/genetics.117.300537
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发表时间：
2018-01
期刊：
影响因子：
3.3
通讯作者：
Guacci V
中科院分区：
文献类型：
--
作者：
Bloom MS;Koshland D;Guacci V
粘着蛋白系留DNA以介导姐妹染色单体粘着、染色体凝聚和DNA修复。细胞如何调节粘附素来执行这些不同的功能仍有待阐明。一种粘着蛋白调节剂，Wpl 1 p，其特征在于在酿酒酵母中作为有效凝聚的促进剂和凝聚的抑制剂。Wpl 1 p也是抵抗DNA损伤剂所必需的。在这里，我们提供的证据表明，Wpl 1 p促进S期诱导的DNA损伤的及时修复。先前的研究表明，Wpl 1 p通过调节粘附素亚基Mcd 1 p和Smc 3 p之间的界面来破坏粘附素与DNA的结合。我们的研究结果表明，Wpl 1 p可能会调节这个接口，以调节所有的粘蛋白的生物学功能。此外，我们表明，Wpl 1 p调节凝聚力和凝聚力，通过形成一个功能复合物与另一个凝聚素相关的因素，Pds 5 p。相反，Wpl 1 p调节DNA修复独立于其与Pds 5 p的相互作用。总之，这些结果表明，Wpl 1 p调节不同的生物学功能的粘附Pds 5 p依赖性和非依赖性调制的Smc 3 p/Mcd 1 p接口。
Cohesin tethers DNA to mediate sister chromatid cohesion, chromosome condensation, and DNA repair. How the cell regulates cohesin to perform these distinct functions remains to be elucidated. One cohesin regulator, Wpl1p, was characterized in Saccharomyces cerevisiae as a promoter of efficient cohesion and an inhibitor of condensation. Wpl1p is also required for resistance to DNA-damaging agents. Here, we provide evidence that Wpl1p promotes the timely repair of DNA damage induced during S-phase. Previous studies have indicated that Wpl1p destabilizes cohesin’s binding to DNA by modulating the interface between the cohesin subunits Mcd1p and Smc3p. Our results suggest that Wpl1p likely modulates this interface to regulate all of cohesin’s biological functions. Furthermore, we show that Wpl1p regulates cohesion and condensation through the formation of a functional complex with another cohesin-associated factor, Pds5p. In contrast, Wpl1p regulates DNA repair independently of its interaction with Pds5p. Together, these results suggest that Wpl1p regulates distinct biological functions of cohesin by Pds5p-dependent and -independent modulation of the Smc3p/Mcd1p interface.
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影响因子：
64.5
作者：
Haarhuis JHI;van der Weide RH;Blomen VA;Yáñez-Cuna JO;Amendola M;van Ruiten MS;Krijger PHL;Teunissen H;Medema RH;van Steensel B;Brummelkamp TR;de Wit E;Rowland BD
通讯作者：
Rowland BD
影响因子：
5.3
作者：
AVEMANN, K;KNIPPERS, R;SOGO, JM
通讯作者：
SOGO, JM
影响因子：
14.9
作者：
Challa K;Lee MS;Shinohara M;Kim KP;Shinohara A
通讯作者：
Shinohara A
影响因子：
3.3
作者：
Guacci V;Koshland D
通讯作者：
Koshland D
影响因子：
3.3
作者：
Guacci V;Stricklin J;Bloom MS;Guō X;Bhatter M;Koshland D
通讯作者：
Koshland D