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Nek1 Regulates Rad54 to Orchestrate Homologous Recombination and Replication Fork Stability.

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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Spies J,Waizenegger A,Barton O,Sürder M,Wright WD,Heyer WD,Löbrich M

doi

10.1016/j.molcel.2016.04.032

subject

Has Abstract

pub_date

2016-06-16 00:00:00

pages

903-917

issue

6

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(16)30108-3

journal_volume

62

pub_type

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