Nek1 Regulates Rad54 to Orchestrate Homologous Recombination and Replication Fork Stability

Julian Spies, Anja Waizenegger, Olivia Barton, Michael Sürder, William D. Wright, Wolf Dietrich Heyer, Markus Löbrich

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31 Scopus citations

Abstract

Never-in-mitosis A-related kinase 1 (Nek1) has established roles in apoptosis and cell cycle regulation. We show that human Nek1 regulates homologous recombination (HR) by phosphorylating Rad54 at Ser572 in late G2 phase. Nek1 deficiency as well as expression of unphosphorylatable Rad54 (Rad54-S572A) cause unresolved Rad51 foci and confer a defect in HR. Phospho-mimic Rad54 (Rad54-S572E), in contrast, promotes HR and rescues the HR defect associated with Nek1 loss. Although expression of phospho-mimic Rad54 is beneficial for HR, it causes Rad51 removal from chromatin and degradation of stalled replication forks in S phase. Thus, G2-specific phosphorylation of Rad54 by Nek1 promotes Rad51 chromatin removal during HR in G2 phase, and its absence in S phase is required for replication fork stability. In summary, Nek1 regulates Rad51 removal to orchestrate HR and replication fork stability.

Original languageEnglish (US)
Pages (from-to)903-917
Number of pages15
JournalMolecular Cell
Volume62
Issue number6
DOIs
StatePublished - Jun 16 2016

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Spies, J., Waizenegger, A., Barton, O., Sürder, M., Wright, W. D., Heyer, W. D., & Löbrich, M. (2016). Nek1 Regulates Rad54 to Orchestrate Homologous Recombination and Replication Fork Stability. Molecular Cell, 62(6), 903-917. https://doi.org/10.1016/j.molcel.2016.04.032