DNA double-strand break resection occurs during non-homologous end joining in G1 but is distinct from resection during homologous recombination

Biehs, Ronja, Steinlage, Monika, Barton, Oliva, Juhász, Szilvia, Künzel, Julia, Spies, Julian, Shibata, Atsushi, Jeggo, Penny and Löbrich, Markus (2017) DNA double-strand break resection occurs during non-homologous end joining in G1 but is distinct from resection during homologous recombination. Molecular Cell, 65 (4). pp. 671-684. ISSN 1097-2765

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Abstract

Canonical non-homologous end joining (c-NHEJ) repairs DNA double-strand breaks (DSBs) in G1 cells with biphasic kinetics. We show that DSBs repaired with slow kinetics, including those localizing to heterochromatic regions or harboring additional lesions at the DSB site, undergo resection prior to repair by c-NHEJ and not alt-NHEJ. Resection-dependent c-NHEJ represents an inducible process during which Plk3 phosphorylates CtIP, mediating its interaction with Brca1 and promoting the initiation of resection. Mre11 exonuclease, EXD2, and Exo1 execute resection, and Artemis endonuclease functions to complete the process. If resection does not commence, then repair can ensue by c-NHEJ, but when executed, Artemis is essential to complete resection-dependent c-NHEJ. Additionally, Mre11 endonuclease activity is dispensable for resection in G1. Thus, resection in G1 differs from the process in G2 that leads to homologous recombination. Resection-dependent c-NHEJ significantly contributes to the formation of deletions and translocations in G1, which represent important initiating events in carcinogenesis.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups: Genome Damage and Stability Centre
Subjects: Q Science
Depositing User: Penny Jeggo
Date Deposited: 16 Aug 2018 11:00
Last Modified: 16 Aug 2018 11:01
URI: http://srodev.sussex.ac.uk/id/eprint/60346

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Project NameSussex Project NumberFunderFunder Ref
RDF8: Identifying the origin of translocation-prone, ATM dependent DNA double-strand breaks using chromatin immunoprecipitation mass spectrometryUnsetUNIVERSITY OF SUSSEXRDF8-008