CENP-A Ubiquitylation Is Indispensable to Cell Viability

Yohei Niikura, Risa Kitagawa, Lei Fang, Katsumi Kitagawa

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity, but how CENP-A is deposited at the centromere remains obscure. We previously reported that CENP-A K124 ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere. However, a recent report stated that CENP-A K124R mutants show no defects in centromere localization and cell viability. In the present study, we found that EYFP tagging induces additional ubiquitylation of EYFP-CENP-A K124R, which allows the mutant protein to bind to HJURP. Using a previously developed conditional CENP-A knockout system and our CENP-A K124R knockin mutant created by the CRISPR-Cas9 system, we show that the Flag-tagged or untagged CENP-A K124R mutant is lethal. This lethality is rescued by monoubiquitin fusion, indicating that CENP-A ubiquitylation is essential for viability.

Original languageEnglish (US)
Pages (from-to)683-689.e6
JournalDevelopmental Cell
Volume50
Issue number6
DOIs
StatePublished - Sep 23 2019

Keywords

  • CENP-A
  • centromere
  • centromere identity
  • conditional knockout system
  • epigenetics
  • kinetochore
  • mitosis
  • monoubiquitin
  • posttranslational modifications (PTMs)
  • ubiquitylation

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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