SPINDOC functions as a mitotic molecular counter to coordinate spatiotemporal CENP-A assembly.

Authors

Zixu Zhang, Xuechun Zhang, Yuting Liu, Kehui Wang, Zhen Chen, Sheng Zhang, Li Huang, Zihan Ma, Changrong Shao, Yuqin Han, Zhouliang Yu, Xiaodong Zhang, Zan Huang, Haiyan Lin, Guohong Li

Published in

Cell reports. Volume 45. Issue 7. Pages 117588. Jun 22, 2026. Epub Jun 22, 2026.

Abstract

Cell cycle-dependent maintenance of centromere protein A (CENP-A) levels and its spatiotemporal assembly are essential for centromere propagation. CENP-A synthesis peaks in late G2, while its assembly occurs during late telophase/early G1. We have previously shown that phosphorylation of CENP-A at Ser68 by CDK1-cyclin B during mitosis impairs its binding to holiday junction recognition protein (HJURP) and facilitates DCAF11-dependent polyubiquitination and degradation. However, the mechanisms governing CENP-A^pS68 stability remain elusive. Here, we demonstrate that spindlin interactor and repressor of chromatin binding (SPINDOC), as an M-phase-specific maintenance factor for CENP-A assembly, binds and stabilizes CENP-A^pS68 by antagonizing DCAF11-dependent polyubiquitination. In addition, SPINDOC bridges CENP-A^pS68 to HJURP, ensuring that CENP-A^pS68 is poised for subsequent deposition at centromeres. Interestingly, SPINDOC promotes liver cancer development in vitro and in vivo, and alterations in its levels disrupt CENP-A^pS68 homeostasis, resulting in chromosomal instability. Together, this study identifies SPINDOC as a mitotic molecular counter of newly synthesized CENP-A, coordinating its spatiotemporal assembly by presenting it to HJURP.

PMID:
42329769
Bibliographic data and abstract were imported from PubMed on 23 Jun 2026.

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