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A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice.

Escribano-Díaz C ¹,

Fradet-Turcotte A ,

Affiliations

1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Authors
Escribano-Díaz C¹
(1 author)

ORCIDs linked to this article

Molecular Cell, 17 Jan 2013, 49(5):872-883
https://doi.org/10.1016/j.molcel.2013.01.001 PMID: 23333306

A comment on this article appears in "RIF1 in DNA break repair pathway choice." Mol Cell. 2013 Mar 7;49(5):840-1.

Abstract

DNA double-strand break (DSB) repair pathway choice is governed by the opposing activities of 53BP1 and BRCA1. 53BP1 stimulates nonhomologous end joining (NHEJ), whereas BRCA1 promotes end resection and homologous recombination (HR). Here we show that 53BP1 is an inhibitor of BRCA1 accumulation at DSB sites, specifically in the G1 phase of the cell cycle. ATM-dependent phosphorylation of 53BP1 physically recruits RIF1 to DSB sites, and we identify RIF1 as the critical effector of 53BP1 during DSB repair. Remarkably, RIF1 accumulation at DSB sites is strongly antagonized by BRCA1 and its interacting partner CtIP. Lastly, we show that depletion of RIF1 is able to restore end resection and RAD51 loading in BRCA1-depleted cells. This work therefore 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.

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Read article at publisher's site: https://doi.org/10.1016/j.molcel.2013.01.001

Read article for free, from open access legal sources, via Unpaywall: http://www.cell.com/article/S1097276513000026/pdf

References

Articles referenced by this article (31)

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Article citations

OTUD5 promotes end-joining of deprotected telomeres by promoting ATM-dependent phosphorylation of KAP1<sup>S824</sup>.
Lam SY, van der Lugt R, Cerutti A, Yalçin Z, Thouin AM, Simonetta M, Jacobs JJL
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53BP1 deficiency leads to hyperrecombination using break-induced replication (BIR).
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Kilgas S, Syed A, Toolan-Kerr P, Swift ML, Roychoudhury S, Sarkar A, Wilkins S, Quigley M, Poetsch AR, Botuyan MV, Cui G, Mer G, Ule J, Drané P, Chowdhury D
Nat Commun, 15(1):8438, 30 Sep 2024
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Data

Data that cites the article

This data has been provided by curated databases and other sources that have cited the article.

Gene Ontology Annotation Project

https://www.ebi.ac.uk/QuickGO/annotations?reference=23333306

Proteins in UniProt (Showing 5 of 70)

BRCT domain-containing protein(UniProt - A0A5H1ZRL7)
cDNA FLJ78617(UniProt - A8KA50)
BRCT domain-containing protein(UniProt - B3KVT9)
Tumor protein p53(UniProt - A0A0R9RRX7)
Replication timing regulatory factor 1(UniProt - A0A2I3BQ21)

Go to all (70) records in UniProt

GlyGen is an international glycobioinformatics knowledgebase funded by The National Institutes of Health to facilitate glycoscience research by integrating diverse kinds of information, including glycomics, genomics, proteomics (and glycoproteomics), cell biology, developmental biology and biochemistry.

https://www.glygen.org/publication/MED/23333306

Mouse Genome Informatics (MGI)

http://www.informatics.jax.org/reference/23333306

Protein families in InterPro (3)

BRCT_p53bp1-like_rpt1(InterPro - IPR047249)
BRCT_p53bp1-like_rpt2(InterPro - IPR047250)
TP53BP1-like(InterPro - IPR047252)

Reactome (2)

WikiPathways (2)

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Funding

Funders who supported this work.

Canadian Institutes of Health Research (1)

Grant ID: MOP84297
2 publications