Analysis of the molecular mechanism and structural basis of the chromosome condensation protein, condensin

染色体缩合蛋白condensin的分子机制和结构基础分析

基本信息

批准号：
18570188
负责人：
KIMURA Keiji
金额：
$ 2.63万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18570188/
关键词：
condensin SMC chromatin mitotic chromosomes ATP 染色体凝縮 SMCタンパク質細胞周期クロマチン構造

项目摘要

Condensin is a conserved five-subunit protein complex composed of SMC heterodimer (SMC2/CAP-E and SMC4/CAP-C) and three other non-SMC subunits, and plays an essential role in mitotic chromosome condensation. Recently, it is reported that condensin is implicated in chromatin regulation during interphase, such as DNA repair, damage checkpoint response and transcriptional regulation. Purified condensin has an activity to introduce positive supercoiles into DNA in the presence of ATP. In higher eukaryotes, two condensin isoform, condensin I and condensin II are expressed.Condensin I is phosphorylated by CK2 during interphase in addition to the mitotic phosphorylation by Cdc2. In contrast to the stimulatory effect of Cdc2-mediated phosphorylation during mitosis, phosphorylation by CK2 reduced the supercoiling activity of condensin I. CK2-mediated phosphorylation of condensin I is spatially and temporally regulated in a manner different to that of Cdc2-mediated phosphorylation: CK2-dependent phosphorylation during Interphase and decreases on chromosomes during mitosis. These finding is the first demonstration of a negative regulatory mode of condensin I.It is also found that PP2A is required for the chromosomal association of condensin II. Interestingly, phosphatase activity of PP2A is not required for chromosomal association of condensin II. PP2A works as a chaperon that brings and localizes condensin II to chromosomes.

凝缩蛋白是一种保守的五亚基蛋白质复合物，由 SMC 异二聚体（SMC2/CAP-E 和 SMC4/CAP-C）和其他三个非 SMC 亚基组成，在有丝分裂染色体凝缩中发挥重要作用。最近有报道称，凝缩蛋白参与间期染色质调控，如DNA修复、损伤检查点反应和转录调控。纯化的凝缩蛋白具有在 ATP 存在下将正超螺旋引入 DNA 的活性。在高等真核生物中，表达两种凝缩蛋白异构体：凝缩蛋白I和凝缩蛋白II。除了Cdc2的有丝分裂磷酸化之外，凝缩蛋白I在间期还被CK2磷酸化。与有丝分裂期间 Cdc2 介导的磷酸化的刺激作用相反，CK2 的磷酸化降低了凝缩蛋白 I 的超螺旋活性。CK2 介导的凝缩蛋白 I 磷酸化的空间和时间调节方式与 Cdc2 介导的磷酸化不同：CK2间期期间的依赖性磷酸化和有丝分裂期间染色体上的减少。这些发现首次证明了凝缩蛋白 I 的负调控模式。还发现 PP2A 是凝缩蛋白 II 染色体关联所必需的。有趣的是，凝缩蛋白 II 的染色体关联不需要 PP2A 的磷酸酶活性。 PP2A 作为伴侣将凝缩蛋白 II 带到染色体上并进行定位。