Abstract
Condensin complexes play crucial roles in chromosome condensation that is a fundamental process to establish the “rod-like” shape of chromosome structure in mitosis. Failure of the chromosome assembly causes chromosome segregation errors and subsequent genomic instability. However, a molecular mechanism that controls condensin function for the chromosomal organization has not been fully understood. Here, we show that the abundance of CAP-H2, one of the condensin II subunits, is fluctuated during the cell cycle in accordance with Plk1 kinase activity. Inhibition of Plk1 leads to Cdc20-mediated degradation of CAP-H2 in mitosis. Plk1 phosphorylation of CAP-H2 at Ser288 is required for the accumulation of CAP-H2 and accurate chromosomal condensation during prophase. These findings suggest that Plk1 phosphorylation regulates condensin II function by modulating CAP-H2 expression levels to facilitate proper mitotic chromosome organization.
Highlights
Chromosomal morphology is drastically changed during the cell division cycle
To confirm that CAP-H2 is increased during normal mitotic progression, HeLa cells were synchronized at G1/S phase by thymidine and released into cell cycle
Depletion of Plk[1] by siRNA suppressed the mitotic CAP-H2 expression (Supplemental Fig. S1E). These results suggest that the abundance of CAP-H2 is controlled by Plk[1] kinase activity during mitosis
Summary
Chromosomal morphology is drastically changed during the cell division cycle. The “rod-like” shape of mitotic chromosome structure enables discrimination of the individual chromosome. Previous studies have reported that condensin subunits are highly phosphorylated during mitosis and several mitotic kinases regulate condensin functions[2] In this context, Cdk[1] and Plk[1] phosphorylate condensins and induce chromosome condensation[3,4,5,6]. In interphase of Drosophila cells, CAP-H2 protein levels are regulated by Skp-Cullin-F-box (SCF) ubiquitin E3 ligase-mediated degradation, but the SCF target domain of CAP-H2 is found only in Drosophila[10] This finding implies the possibility that the ubiquitination is involved in regulating condensin II function in other organisms; there is no evidence that the subunits of condensin II are regulated by ubiquitin-proteolysis mechanism besides Drosophila. We concluded that the expression levels of CAP-H2 are regulated by Plk[1] and Cdc[20] for proper chromosomal organization during mitosis
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