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

J Cell Sci. 2018 Mar 22;131(6):jcs212092. doi: 10.1242/jcs.212092.

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.

Keywords: AID; Auxin-inducible degron; Condensin; Ki-67; Mitotic chromosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Chromosomes, Human / genetics
  • Chromosomes, Human / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Indoleacetic Acids / metabolism
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism*
  • Mitosis*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Protein Transport

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Indoleacetic Acids
  • Ki-67 Antigen
  • Multiprotein Complexes
  • Nuclear Proteins
  • SMC2 protein, human
  • condensin complexes
  • Adenosine Triphosphatases