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

Barton, Olivia ; Naumann, Steffen C. ; Diemer-Biehs, Ronja ; Künzel, Julia ; Steinlage, Monika ; Conrad, Sandro ; Makharashvili, Nodar ; Wang, Jiadong ; Feng, Lin ; Lopez, Bernard S. ; Paull, Tanya T. ; Chen, Junjie ; Jeggo, Penny A. ; Löbrich, Markus (2021):
Polo-like kinase 3 regulates CtIP during DNA double-strand break repair in G1. (Publisher's Version)
In: Journal of Cell Biology, 206 (7), pp. 877-894. Rockefeller University Press, ISSN 0021-9525, e-ISSN 1540-8140,
DOI: 10.26083/tuprints-00018937,
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Item Type: Article
Origin: Secondary publication service
Status: Publisher's Version
Title: Polo-like kinase 3 regulates CtIP during DNA double-strand break repair in G1
Language: English
Abstract:

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.

Journal or Publication Title: Journal of Cell Biology
Journal volume: 206
Number: 7
Publisher: Rockefeller University Press
Classification DDC: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Divisions: 10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 07 Sep 2021 12:07
Last Modified: 07 Sep 2021 12:07
DOI: 10.26083/tuprints-00018937
Corresponding Links:
URN: urn:nbn:de:tuda-tuprints-189376
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/18937
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