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Science 339 (6120): 700-704

Copyright © 2013 by the American Association for the Advancement of Science

53BP1 Regulates DSB Repair Using Rif1 to Control 5' End Resection

Michal Zimmermann,1,2 Francisca Lottersberger,1 Sara B. Buonomo,3 Agnel Sfeir,1,* Titia de Lange1,{dagger}

Abstract: The choice between double-strand break (DSB) repair by either homology-directed repair (HDR) or nonhomologous end joining (NHEJ) is tightly regulated. Defects in this regulation can induce genome instability and cancer. 53BP1 is critical for the control of DSB repair, promoting NHEJ, and inhibiting the 5' end resection needed for HDR. Using dysfunctional telomeres and genome-wide DSBs, we identify Rif1 as the main factor used by 53BP1 to impair 5' end resection. Rif1 inhibits resection involving CtIP, BLM, and Exo1; limits accumulation of BRCA1/BARD1 complexes at sites of DNA damage; and defines one of the mechanisms by which 53BP1 causes chromosomal abnormalities in Brca1-deficient cells. These data establish Rif1 as an important contributor to the control of DSB repair by 53BP1.

1 Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY 10065, USA.
2 Central European Institute of Technology and Faculty of Science, Masaryk University, Brno, Czech Republic.
3 European Molecular Biology Laboratory, Mouse Biology Unit, Monterotondo, Italy.

* Present address: Developmental Genetics Program and Department of Cell Biology, Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.

{dagger} To whom correspondence should be addressed. E-mail: delange{at}mail.rockefeller.edu


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