J Cell Biol-2014-Barton-877-94.pdf (5.94 MB)
Polo-like kinase 3 regulates CtIP during DNA double-strand break repair in G1
journal contribution
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 LöbrichDNA 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 BiologyISSN
0021-9525Publisher
Rockefeller University PressExternal DOI
Issue
7Volume
206Page range
877-894Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2016-01-18First Open Access (FOA) Date
2016-01-18First Compliant Deposit (FCD) Date
2016-01-18Usage metrics
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