Separase biosensor reveals that cohesin cleavage timing depends on phosphatase PP2A(Cdc55) regulation.
Separase biosensor reveals that cohesin cleavage timing depends on phosphatase PP2A(Cdc55) regulation.
复制标题
分离酶生物传感器揭示粘连蛋白裂解时间取决于磷酸酶 PP2A(Cdc55) 调节。
DOI：
10.1016/j.devcel.2012.06.007
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发表时间：
2012
影响因子：
11.8
通讯作者：
Morgan,DavidO
中科院分区：
文献类型：
--
作者：
Yaakov,Gilad;Thorn,Kurt;Morgan,DavidO
在分裂后期，姐妹染色单体突然分离，然后被有丝分裂纺锤体分离。蛋白酶分离酶通过切割将姐妹篇结合在一起的粘附素环的Scc 1/Mcd 1亚基来触发姐妹分离。Scc 1的Polo激酶磷酸化促进其裂解，但其潜在的调控回路尚不清楚。我们开发了一种酵母分离酶生物传感器，提供了一个定量指标的cohesin切割在单细胞。分离酶被突然激活，并在1分钟内切割大多数粘附素，之后后期开始。着丝粒和端粒附近的粘着蛋白以相同的速度和时间被切割。蛋白磷酸酶PP 2ACdc 55通过抵消Scc 1的polo激酶磷酸化抑制粘附素切割。在后期早期，先前描述的PP 2ACdc 55的分离酶抑制促进粘着蛋白切割。因此，分离酶直接作用于Scc 1，也间接地，通过抑制PP 2ACdc 55，以刺激粘连蛋白裂解，提供一个前馈回路，可能有助于一个强大的和及时的后期。
In anaphase, sister chromatids separate abruptly and are then segregated by the mitotic spindle. The protease separase triggers sister separation by cleaving the Scc1/Mcd1 subunit of the cohesin ring that holds sisters together. Polo-kinase phosphorylation of Scc1 promotes its cleavage, but the underlying regulatory circuits are unclear. We developed a separase biosensor inSaccharomyces cerevisiaethat provides a quantitative indicator of cohesin cleavage in single cells. Separase is abruptly activated and cleaves most cohesin within 1 min, after which anaphase begins. Cohesin near centromeres and telomeres is cleaved at the same rate and time. Protein phosphatase PP2ACdc55inhibits cohesin cleavage by counteracting polo-kinase phosphorylation of Scc1. In early anaphase, the previously described separase inhibition of PP2ACdc55promotes cohesin cleavage. Thus, separase acts directly on Scc1 and also indirectly, through inhibition of PP2ACdc55, to stimulate cohesin cleavage, providing a feedforward loop that may contribute to a robust and timely anaphase.