CENP-C-Mis12 complex establishes a regulatory loop through Aurora B for chromosome segregation

Life Sci Alliance. 2024 Oct 21;8(1):e202402927. doi: 10.26508/lsa.202402927. Print 2025 Jan.

Abstract

Establishing the correct kinetochore-microtubule attachment is crucial for faithful chromosome segregation. The kinetochore has various regulatory mechanisms for establishing correct bipolar attachment. However, how the regulations are coupled is not fully understood. Here, we demonstrate a regulatory loop between the kinetochore protein CENP-C and Aurora B kinase, which is critical for the error correction of kinetochore-microtubule attachment. This regulatory loop is mediated through the binding of CENP-C to the outer kinetochore Mis12 complex (Mis12C). Although the Mis12C-binding region of CENP-C is dispensable for mouse development and proliferation in human RPE-1 cells, those cells lacking this region display increased mitotic defects. The CENP-C-Mis12C interaction facilitates the centromeric recruitment of Aurora B and the mitotic error correction in human cells. Given that Aurora B reinforces the CENP-C-Mis12C interaction, our findings reveal a positive regulatory loop between Aurora B recruitment and the CENP-C-Mis12C interaction, which ensures chromosome biorientation for accurate chromosome segregation.

MeSH terms

  • Animals
  • Aurora Kinase B* / metabolism
  • Cell Line
  • Chromosomal Proteins, Non-Histone* / metabolism
  • Chromosome Segregation*
  • Humans
  • Kinetochores* / metabolism
  • Mice
  • Microtubule-Associated Proteins
  • Microtubules / metabolism
  • Mitosis
  • Protein Binding

Substances

  • Aurora Kinase B
  • Chromosomal Proteins, Non-Histone
  • AURKB protein, human
  • centromere protein C
  • MIS12 protein, human
  • Aurkb protein, mouse
  • Microtubule-Associated Proteins