2014年8月31日 · Our results establish a competition between Sgo1 and Wapl in cohesin binding and implicate a role for this direct antagonism in centromeric cohesion protection. We coexpressed human SA2 and the...

2012年12月16日 · Timely dissolution of sister-chromatid cohesion in mitosis ensures accurate chromosome segregation to guard against aneuploidy and tumorigenesis. The complex of shugoshin and protein phosphatase 2A...

2023年4月20日 · SGO1 protects centromeric cohesin by recruiting PP2A to counteract cohesin phosphorylation by mitotic kinases, and SGO1 also directly competes with WAPL for cohesin binding 15,16,17,18.

The two-tier modular regulation of Wapl interaction with Scc1-SA2 ensures that Wapl is dominant over Sgo1, as well as the FDF motif-containing inner kinetochore protein CENP-U , for binding Scc1-SA2, thereby enabling removal of the bulk of Cohesin from chromosome arms to ensure precise chromosome segregation.

2024年8月23日 · 本项研究利用一系列体内外蛋白互作实验，以及基于AlphaFold2的人工智能蛋白质结构分析，发现Wapl分别通过FGF基序和YNARHWN基序结合黏连蛋白核心亚基Scc1与SA2互作界面的不同区域（图3）。 破坏FGF基序或 YNARHWN基序与Scc1-SA2界面的结合，仅部分减弱Wapl与Scc1-SA2界面的结合，并部分削弱Wapl从染色体上移除黏连蛋白的能力。...

2013年6月17日 · Wapl inactivation alleviates both the requirement for sororin in cohesion establishment in S phase and the need for Sgo1–PP2A in centromeric cohesion protection in mitosis (6, 7, 15, 24). Thus, Wapl is a critical negative regulator of cohesin.

2013年10月21日 · Stable WAPL depletion arrests cells in a p53-dependent manner but causes p53-deficient cells to become highly aneuploid. Our data show that the WAPL-dependent prophase pathway is essential for proper chromosome segregation and is crucial to maintain genomic integrity.

2009年9月15日 · We propose that Wapl and Pds5 directly modulate conformational changes of cohesin to make it competent for dissociation from chromatin during prophase. Evidence is also presented that Sgo1 plays a hitherto underappreciated role in stabilizing cohesin along chromosome arms, which is antagonized by the mitotic kinases polo-like kinsase (Plk1) and ...

During prophase, mitotic kinases phosphorylate cohesin and its protector sororin, triggering Wapl-dependent cohesin release from chromosome arms. The shugoshin (Sgo1)-PP2A complex protects centromeric cohesin until its cleavage by separase at anaphase onset. Here, we report the crystal structure of a human cohesin subcomplex comprising SA2 and ...

2024年8月12日 · 黏连蛋白环的DNA出口（即Smc3-Scc1互作界面）的开放依赖于黏连蛋白释放因子Wapl【2-4】。 一个长期悬而未决的科学问题是，Wapl如何打开黏连蛋白环的DNA出口进而调控黏连蛋白功能，而解决这个问题的关键在于探明Wapl如何结合黏连蛋白复合体的核心亚基。