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bioRxiv · 10.1101/2021.11.23.469796

Ser68 phosphoregulation is essential for CENP-A deposition, centromere function and viability in mice

Liu, Y.·Wang, K.·Huang, L.·Zhao, J.·Chen, X.·Wu, Q.·Yu, Z.·Li, G.
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Abstract

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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Liu, Y., Wang, K., Huang, L., Zhao, J., Chen, X., Wu, Q., Yu, Z., Li, G.. 2021-11-24. Ser68 phosphoregulation is essential for CENP-A deposition, centromere function and viability in mice. https://doi.org/10.1101/2021.11.23.469796

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