A novel mechanism that regulates decondensation of mitotic chromosomes

Microbial Genetics Laboratory / Niki Group

Release of condensin from mitotic chromosomes requires the Ran-GTP gradient in the reorganized nucleus.

Keita Aoki and Hironori Niki

Biology Open, November 15; 6(11):1614-1628, 2017 DOI:10.1242/bio.027193.

After mitosis, nuclear reorganization occurs together with decondensation of mitotic chromosomes and reformation of the nuclear envelope, thereby restoring the Ran-GTP gradient between nucleus and cytoplasm. The Ran-GTP gradient is dependent on Pim1/RCC1. Interestingly, a defect in Pim1/RCC1 in Schizosaccharomyces pombe causes post-mitotic condensation of chromatin, namely hyper-condensation, suggesting a relationship between the Ran-GTP gradient and chromosome decondensation. However, how Ran-GTP interacts with chromosome decondensation is unresolved. To examine this interaction, we used Schizosaccharomyces japonicus, which is known to undergo partial breakdown of the nuclear membrane during mitosis. We found that Pim1/RCC1 was localized on nuclear pores, but this localization failed in a temperature-sensitive mutant of Pim1/RCC1. The mutant cells exhibited hyper-condensed chromatin after mitosis due to prolonged association of condensin on the chromosomes. Conceivably, a condensin-dephosphorylation defect might cause hyper-condensed chromatin, since chromosomal localization of condensin is dependent on phosphorylation by cyclin-dependent kinase (CDK). Indeed, CDK-phospho-mimic mutation of condensin alone caused untimely condensin localization, resulting in hyper-condensed chromatin. Together, these results suggest that dephosphorylation of CDK sites of condensin might require the Ran-GTP gradient produced by nuclear pore-localized Pim1/RCC1.

Figure1

In a normal-sized nucleus (left), condensin is released from chromosomes in a Ran-GTP dependent manner. Therefore, a decondensed chromatin is formed in G1 phase. In a Pim1/RCC1-deficient nucleus, condensin is not released from chromosomes due to few Ran-GTP. Therefore, a hyper-condensed chromatin is formed in G1 phase.