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

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...

Full description

Saved in:
Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2013-02, Vol.339 (6120), p.700-704
Main Authors: Zimmermann, Michal, Lottersberger, Francisca, Buonomo, Sara B., Sfeir, Agnel, de Lange, Titia
Format: Article
Language:English
Subjects:
Alleles
Animals
BRCA1 Protein - metabolism
Breaking
Cancer
Cell lines
Cells, Cultured
Chromosomal Proteins, Non-Histone - chemistry
Chromosomal Proteins, Non-Histone - genetics
Chromosomal Proteins, Non-Histone - metabolism
Chromosomes
Damage
Deoxyribonucleic acid
DNA - metabolism
DNA Breaks, Double-Stranded
DNA damage
DNA End-Joining Repair
DNA Repair
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Final causes
Flowering
Flowers
Genomics
Immunoglobulins
Mice
Online
Plants
Proteins
Quantification
Repair
Replication Protein A - metabolism
Signals
Switching
Telomere - metabolism
Telomere-Binding Proteins - metabolism
Telomeres
Telomeric Repeat Binding Protein 2 - genetics
Telomeric Repeat Binding Protein 2 - metabolism
Tumor Suppressor p53-Binding Protein 1
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1231573