RIF1 Is Essential for 53BP1-Dependent Nonhomologous End Joining and Suppression of DNA Double-Strand Break Resection
By Ross Chapman, P. Barral, Jean-Baptiste Vannier, V. Borel, Martin Steger, Antonia Tomás‐Loba, A. Sartori, I. Adams, F. Batista, S. Boulton. Molecules and Cells, 2013
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Summary The appropriate execution of DNA double-strand break (DSB) repair is critical for genome stability and tumor avoidance. 53BP1 and BRCA1 directly influence DSB repair pathway choice by regulating 5′ end resection, but how this is achieved remains uncertain. Here we report that Rif1−/− mice are severely compromised for 53BP1-dependent class switch recombination (CSR) and fusion of dysfunctional telomeres. The inappropriate accumulation of RIF1 at DSBs in S phase is antagonized by BRCA1, and deletion of Rif1 suppresses toxic nonhomologous end joining (NHEJ) induced by PARP inhibition in Brca1-deficient cells. Mechanistically, RIF1 is recruited to DSBs via the N-terminal phospho-SQ/TQ domain of 53BP1, and DSBs generated by ionizing radiation or during CSR are hyperresected in the absence of RIF1. Thus, RIF1 and 53BP1 cooperate to block DSB resection to promote NHEJ in G1, which is antagonized by BRCA1 in S phase to ensure a switch of DSB repair mode to homologous recombination.
Subfields: Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/8e0327c8e513cb28dd0a174214f77aef7e68ee6b
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Citations in the corpus
- Repair of strand breaks by homologous recombination. (2013, background): “Several laboratories have recently described the RIF1 protein as an effector of DNA end resection control by 53BP1 (Chapman et al. 2013; Di Virgilio et al. 2013; EscribanoDiaz et al. 2013; Feng et al. 2013; Zimmermann et al. 2013).”
- Homologous recombination and human health: the roles of BRCA1, BRCA2 and associated proteins (2015, background): “2013) and also involves RIF1, which binds ATM-phosphorylated 53BP1 (Chapman et al. 2013; Escribano-Diaz et al. 2013; Feng et al. 2013; Zimmermann et al. 2013).”
- 53BP1 is a reader of the DNA damage-induced H2A Lys15 ubiquitin mark (2013, positive): “Class switching to IgG1 was assayed in 53BP1 murine primary B cells complemented with 53BP1 (1-1711) and mutants thereof by retroviral delivery.”
- Repair Pathway Choices and Consequences at the Double-Strand Break (2015, neutral): “This end protection function of 53BP1 depends upon its phosphorylation by activated Ataxia Telangiectasia Mutated (ATM), which promotes the recruitment of interacting factors Rif1 and PTIP, and subsequent recruitment of downstream nucleases such as Artemis [28–31].”