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Polo-like kinase 3 regulates CtIP during DNA double-strand break repair in G1

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posted on 2023-06-09, 00:04 authored by Olivia Barton, Steffen C Naumann, Ronja Diemer-Biehs, Julia Kunzel, Monika Steinlage, Sandro Conrad, Nodar Makharashvili, Jiadong Wang, Lin Feng, Bernard S Lopez, Tanya T Paull, Junji Chen, Penny Jeggo, Markus Löbrich
DNA double-strand breaks (DSBs) are repaired by nonhomologous end joining (NHEJ) or homologous recombination (HR). The C terminal binding protein–interacting protein (CtIP) is phosphorylated in G2 by cyclin-dependent kinases to initiate resection and promote HR. CtIP also exerts functions during NHEJ, although the mechanism phosphorylating CtIP in G1 is unknown. In this paper, we identify Plk3 (Polo-like kinase 3) as a novel DSB response factor that phosphorylates CtIP in G1 in a damage-inducible manner and impacts on various cellular processes in G1. First, Plk3 and CtIP enhance the formation of ionizing radiation-induced translocations; second, they promote large-scale genomic deletions from restriction enzyme-induced DSBs; third, they are required for resection and repair of complex DSBs; and finally, they regulate alternative NHEJ processes in Ku-/- mutants. We show that mutating CtIP at S327 or T847 to nonphosphorylatable alanine phenocopies Plk3 or CtIP loss. Plk3 binds to CtIP phosphorylated at S327 via its Polo box domains, which is necessary for robust damage-induced CtIP phosphorylation at S327 and subsequent CtIP phosphorylation at T847.

History

Publication status

  • Published

File Version

  • Published version

Journal

Journal of Cell Biology

ISSN

0021-9525

Publisher

Rockefeller University Press

Issue

7

Volume

206

Page range

877-894

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2016-01-18

First Open Access (FOA) Date

2016-01-18

First Compliant Deposit (FCD) Date

2016-01-18

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