Rif1 provides a new DNA-binding interface for the Bloom syndrome complex to maintain normal replication
Dongyi Xu,Parameswary A. Muniandy,Elisabetta Leo,Jinhu Yin,Saravanabhavan Thangavel,Xi Shen,Miki,Keli Agama,Rong Guo,David A. Fox,Amom Ruhikanta Meetei,Lauren E. Wilson,Huy Nguyen,Nan Ping Weng,Steven J. Brill,Lei Li,Alessandro Vindigni,Yves Pommier,Michael M. Seidman,Weidong Wang +19 more
TLDR
V vertebrate Rif1 contains a DNA‐binding domain that resembles the αCTD domain of bacterial RNA polymerase α; and this domain preferentially binds fork and Holliday junction (HJ) DNA in vitro and is required for R if1 to resist replication stress in vivo.Abstract:
BLM, the helicase defective in Bloom syndrome, is part of a multiprotein complex that protects genome stability. Here, we show that Rif1 is a novel component of the BLM complex and works with BLM to promote recovery of stalled replication forks. First, Rif1 physically interacts with the BLM complex through a conserved C-terminal domain, and the stability of Rif1 depends on the presence of the BLM complex. Second, Rif1 and BLM are recruited with similar kinetics to stalled replication forks, and the Rif1 recruitment is delayed in BLM-deficient cells. Third, genetic analyses in vertebrate DT40 cells suggest that BLM and Rif1 work in a common pathway to resist replication stress and promote recovery of stalled forks. Importantly, vertebrate Rif1 contains a DNA-binding domain that resembles the αCTD domain of bacterial RNA polymerase α; and this domain preferentially binds fork and Holliday junction (HJ) DNA in vitro and is required for Rif1 to resist replication stress in vivo. Our data suggest that Rif1 provides a new DNA-binding interface for the BLM complex to restart stalled replication forks.read more
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Journal ArticleDOI
Double-strand break repair: 53BP1 comes into focus
TL;DR: A model is emerging in which 53BP1 recruitment requires the direct recognition of a DSB-specific histone code and its influence on pathway choice is mediated by mutual antagonism with breast cancer 1 (BRCA1).
Journal ArticleDOI
A Cell Cycle-Dependent Regulatory Circuit Composed of 53BP1-RIF1 and BRCA1-CtIP Controls DNA Repair Pathway Choice
Cristina Escribano-Diaz,Alexandre Orthwein,Amélie Fradet-Turcotte,Mengtan Xing,Jordan T.F. Young,Jordan T.F. Young,Jan Tkac,Jan Tkac,Michael A Cook,Michael A Cook,Adam P. Rosebrock,Meagan Munro,Marella D. Canny,Dongyi Xu,Daniel Durocher,Daniel Durocher +15 more
TL;DR: This work identifies a cell cycle-regulated circuit, underpinned by RIF1 and BRCA1, that governs DSB repair pathway choice to ensure that NHEJ dominates in G1 and HR is favored from S phase onward.
Journal ArticleDOI
RIF1 Is Essential for 53BP1-Dependent Nonhomologous End Joining and Suppression of DNA Double-Strand Break Resection
J. Ross Chapman,Patricia Barral,Jean-Baptiste Vannier,Valerie Borel,Martin Steger,Antonia Tomás-Loba,Alessandro A. Sartori,Ian R. Adams,Facundo D. Batista,Simon J. Boulton +9 more
TL;DR: Rif1−/− mice are severely compromised for 53BP1-dependent class switch recombination (CSR) and fusion of dysfunctional telomeres and deletion of Rif1 suppresses toxic nonhomologous end joining (NHEJ) induced by PARP inhibition in Brca1-deficient cells.
Journal ArticleDOI
Rif1 Prevents Resection of DNA Breaks and Promotes Immunoglobulin Class Switching
Michela Di Virgilio,Elsa Callen,Arito Yamane,Wenzhu Zhang,Mila Jankovic,Alexander D. Gitlin,Niklas Feldhahn,Wolfgang Resch,Thiago Y. Oliveira,Thiago Y. Oliveira,Thiago Y. Oliveira,Brian T. Chait,André Nussenzweig,Rafael Casellas,Davide F. Robbiani,Michel C. Nussenzweig,Michel C. Nussenzweig +16 more
TL;DR: Rap1-interacting factor 1 (Rif1) is identified as an ATM (ataxia-telangiectasia mutated) phosphorylation-dependent interactor of 53BP1 and it is shown that absence of Rif1 results in 5′-3′ DNA-end resection in mice.
Journal ArticleDOI
53BP1: pro choice in DNA repair
TL;DR: New data revealing how 53BP1 is loaded onto chromatin and uses its interacting factors Rif1 and PTIP to promote NHEJ and inhibit HDR are discussed.
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