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

凝集素是由SMC异源二聚体(SMC2/CAP-E和SMC4/CAP-C)和其他3个非SMC亚基组成的保守的5个亚基蛋白质复合体，在有丝分裂染色体凝聚中起重要作用。最近的研究表明，凝聚素参与了间期染色质的调控，如DNA修复、损伤检查点反应和转录调控。纯化的凝聚素具有在三磷酸腺苷存在下将阳性超螺旋引入DNA的活性。在高等真核生物中，表达两种凝聚素亚型，即凝聚素I和凝聚素II，凝聚素I在分裂间期被CK2磷酸化，有丝分裂过程中的凝聚素I被Cdc2磷酸化。在有丝分裂过程中，CK2的磷酸化降低了凝聚素I的超卷曲活性，而CK2的磷酸化则降低了凝聚素I的超卷曲活性。CK2介导的凝聚素I的磷酸化在空间和时间上受到不同于CDC2介导的磷酸化的调节：间期依赖于CK2的磷酸化，有丝分裂时染色体上的磷酸化减少。这些发现首次证明了凝聚素I的负调控模式。此外，还发现凝聚素II的染色体结合需要PP2A。有趣的是，凝聚素II的染色体结合并不需要PP2A的磷酸酶活性。PP2A作为伴侣将凝聚素II带到染色体并将其定位。

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.