title: 53BP1 regulates DSB repair using Rif1 to control 5' end resection.
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.
authors.affiliation: Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY 10065, USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Francisca
authors.initials: F
authors.lastname: Lottersberger
authors.forename: Sara B
authors.initials: SB
authors.lastname: Buonomo
authors.forename: Agnel
authors.initials: A
authors.lastname: Sfeir
authors.forename: Titia
authors.initials: T
authors.lastname: de Lange
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D051716:Replication Protein A / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D019313:BRCA1 Protein; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D051716:Replication Protein A; C492748:Rif1 protein, mouse; C534796:TRF2 protein, mouse; D034501:Telomere-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2; C498302:Trp53bp1 protein, mouse; D000071857:Tumor Suppressor p53-Binding Protein 1; D004247:DNA