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

Barton, Olivia, Naumann, Steffen C, Diemer-Biehs, Ronja, Kunzel, Julia, Steinlage, Monika, Conrad, Sandro, Makharashvili, Nodar, Wang, Jiadong, Feng, Lin, Lopez, Bernard S, Paull, Tanya T, Chen, Junji, Jeggo, Penny A and Löbrich, Markus (2014) Polo-like kinase 3 regulates CtIP during DNA double-strand break repair in G1. Journal of Cell Biology, 206 (7). pp. 877-894. ISSN 0021-9525

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Penny Jeggo
Date Deposited: 18 Jan 2016 11:57
Last Modified: 18 Jan 2016 11:57
URI: http://srodev.sussex.ac.uk/id/eprint/59283

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