Ki-67 and condensins support the integrity of mitotic chromosomes through distinct mechanisms

Abstract

Although condensins play essential roles in mitotic chromosome assembly, Ki-67 (also known as MKI67), a protein localizing to the periphery of mitotic chromosomes, had also been shown to make a contribution to the process. To examine their respective roles, we generated a set of HCT116-based cell lines expressing Ki-67 and/or condensin subunits that were fused with an auxin-inducible degron for their conditional degradation. Both the localization and the dynamic behavior of Ki-67 on mitotic chromosomes were not largely affected upon depletion of condensin subunits, and vice versa. When both Ki-67 and SMC2 (a core subunit of condensins) were depleted, ball-like chromosome clusters with no sign of discernible thread-like structures were observed. This severe defective phenotype was distinct from that observed in cells depleted of either Ki-67 or SMC2 alone. Our results show that Ki-67 and condensins, which localize to the external surface and the central axis of mitotic chromosomes, respectively, have independent yet cooperative functions in supporting the structural integrity of mitotic chromosomes.

Micromanipulation of prophase I chromosomes from mouse spermatocytes reveals high stiffness and gel-like chromatin organization

“…Meiotic cohesin is present between the arms of sister chromatids through meiotic prophase I 9 . Likewise, condensin can be found compacting mitotic chromosomes along their arms 22,23 . If these complexes formed a contiguous structure through selfattachment or other forms of protein bridging, then the contiguous protein structure would remain between the pipettes after nuclease treatment 30 .…”

“…The protein complexes that act to reorganize chromosomes during mitotic prophase and meiotic prophase I are distinct. The condensin structural maintenance of chromosome (SMC) complex appears to be responsible for much of the morphology and mechanical stiffness of mitotic chromosomes 1,22,23 . The cohesin SMC complex is also present on chromosomes during mitosis, generating sister chromatid cohesion, but it is removed from chromosome arms in mitotic prometaphase, remaining predominately at the centromere 24,25 .…”

Common fragile sites are characterised by faulty condensin loading after replication stress

“…To further investigate the role of condensin using an orthogonal approach, we used HCT116 cell lines in which both copies of CAP-H or CAP-H2 were fused to an AID tag, which enabled rapid depletion of either condensin I or II upon addition of auxin (IAA) for 8 hours (Supplementary Figure 6F) (Takagi et al, 2018).…”

Micromanipulation of prophase I chromosomes from mouse spermatocytes reveals high stiffness and gel-like chromatin organization

“…Future investigations into the SC include the role of synapsis of SYCP1 across meiotic substages and the roles of SYCP2 and SYCP3 2,11,12 . The underlying cohesin core of meiotic chromosomes promises to be an exciting topic for further investigation 6,15,26,27,34 , since when mitotic chromosomes lack condensin, the main mitotic SMC complex, they completely lose their morphology and stiffness 23 . Disruption of the cohesin SMC complex might be expected to drive similar strong effects during meiotic prophase.…”