Journal
SCIENCE CHINA-LIFE SCIENCES
Volume 65, Issue 9, Pages 1881-1889Publisher
SCIENCE PRESS
DOI: 10.1007/s11427-021-2077-1
Keywords
centromere; CENP-A; cell cycle; mitosis; phosphorylation; chromosome segregation
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Funding
- Ministry of Science and Technology of China [2017YFA0504202, 2019YFA0508903]
- National Natural Science Foundation of China [31991161, 32070604]
- Beijing Municipal Science and Technology Committee [Z201100005320013]
- HHMI International Research Scholar grant [55008737]
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The phosphorylation of CENP-A Ser68 is crucial for the cell-cycle-dependent deposition of CENP-A and cell viability.
Centromere identity is defined by nucleosomes containing CENP-A, a histone H3 variant. The deposition of CENP-A at centromeres is tightly regulated in a cell-cycle-dependent manner. We previously reported that the spatiotemporal control of centromeric CENP-A incorporation is mediated by the phosphorylation of CENP-A Ser68. However, a recent report argued that Ser68 phosphoregulation is dispensable for accurate CENP-A loading. Here, we report that the substitution of Ser68 of endogenous CENP-A with either Gln68 or Glu68 severely impairs CENP-A deposition and cell viability. We also find that mice harboring the corresponding mutations are lethal. Together, these results indicate that the dynamic phosphorylation of Ser68 ensures cell-cycle-dependent CENP-A deposition and cell viability.
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