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

Spies, Julian ; Waizenegger, Anja ; Barton, Olivia ; Sürder, Michael ; Wright, William D. ; Heyer, Wolf-Dietrich ; Löbrich, Markus (2016):
Nek1 Regulates Rad54 to Orchestrate Homologous Recombination and Replication Fork Stability.
In: Molecular cell, 62 (6), pp. 903-917. ISSN 1097-4164,
[Article]

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.

Item Type: Article
Erschienen: 2016
Creators: Spies, Julian ; Waizenegger, Anja ; Barton, Olivia ; Sürder, Michael ; Wright, William D. ; Heyer, Wolf-Dietrich ; Löbrich, Markus
Title: Nek1 Regulates Rad54 to Orchestrate Homologous Recombination and Replication Fork Stability.
Language: English
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 or Publication Title: Molecular cell
Journal volume: 62
Number: 6
Divisions: 10 Department of Biology
10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 13 Jun 2016 09:27
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