CENP-A Ubiquitylation Is Indispensable to Cell Viability
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.
Niikura Y, Kitagawa R, Fang L, Kitagawa K. CENP-A Ubiquitylation Is Indispensable to Cell Viability. Dev Cell. 2019 Sep 23;50(6):683-689.e6. doi:
10.1016/j.devcel.2019.07.015. PubMed PMID: 31550462; PubMed Central PMCID:PMC6761987.