2. Academic Validation
  3. KIF18A promotes chromosome congression in cooperation with CENP-E downstream of CENP-C

KIF18A promotes chromosome congression in cooperation with CENP-E downstream of CENP-C

  • Cell Rep. 2025 Nov 25;44(11):116515. doi: 10.1016/j.celrep.2025.116515.
Jiahang Miao 1,  Masatoshi Hara 2,  Kuan-Chung Su 3,  Heather R Keys 3,  Weixia Kong 1,  Yusuke Takenoshita 1,  Iain M Cheeseman 4,  Tatsuo Fukagawa 5
Affiliations

Affiliations

  • 1 Graduate School of Frontier Biosciences, The University of Osaka, Suita, Osaka 565-0871, Japan.
  • 2 Graduate School of Frontier Biosciences, The University of Osaka, Suita, Osaka 565-0871, Japan; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: [email protected].
  • 3 Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA.
  • 4 Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • 5 Graduate School of Frontier Biosciences, The University of Osaka, Suita, Osaka 565-0871, Japan. Electronic address: [email protected].
PMID: 41218610 DOI: 10.1016/j.celrep.2025.116515
Abstract

Chromosome congression is a key process that acts to align chromosomes at the spindle equator via kinetochore-microtubule interactions, with defects in chromosome alignment leading to chromosomal instability. However, defining the mechanisms that underlie chromosome congression is limited due to the multiple factors that act in parallel to regulate chromosome movement. Here, we conducted a genome-wide Cas9-based functional genetics screen using a hypomorphic CENP-C mutant that affects its kinetochore interactions. Our analysis identified KIF18A, whose knockout resulted in synthetic lethality with the CENP-C mutant. Further analysis revealed that the synthetic defect was due to a reduction in CENP-E function in the CENP-C mutant. Our work suggests that KIF18A promotes chromosome alignment in cooperation with CENP-E downstream of CENP-C during early prometaphase. Thus, our analysis enables us to dissect parallel molecular mechanisms for chromosome congression and identify sensitivities and biomarkers that might guide anti-KIF18A chemotherapeutics.

Keywords

CENP-C; CENP-E; CP: Molecular biology; KIF18A; KMN network; kinetochore.

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