53BP1 regulates DSB repair using Rif1 to control 5' end resection

Michal Zimmermann; Francisca Lottersberger; Sara B Buonomo; Agnel Sfeir; Titia de Lange

doi:10.1126/science.1231573

53BP1 regulates DSB repair using Rif1 to control 5' end resection

Michal Zimmermann, Francisca Lottersberger, Sara B Buonomo, Agnel Sfeir, Titia de Lange

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	700-4
Number of pages	5
Journal	Science
Volume	339
Issue number	6120
DOIs	https://doi.org/10.1126/science.1231573
Publication status	Published - 8 Feb 2013

Keywords / Materials (for Non-textual outputs)

animals
BRCA1 protein
cells
chromosomal proteins
DNA
DNA breaks
DNA end-joining repair
DNA repair
DNA-binding proteins
mice
replication protein A
telomere
telomere-binding proteins
telomeric repeat binding protein 2
tumor suppressor p53-binding protein 1
double stranded
non histone
cultured

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10.1126/science.1231573

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@article{2d8417b00964439285759d2a883a1958,

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.",

keywords = "animals, BRCA1 protein, cells, chromosomal proteins, DNA, DNA breaks, DNA end-joining repair, DNA repair, DNA-binding proteins, mice, replication protein A, telomere, telomere-binding proteins, telomeric repeat binding protein 2, tumor suppressor p53-binding protein 1, double stranded, non histone, cultured",

author = "Michal Zimmermann and Francisca Lottersberger and Buonomo, {Sara B} and Agnel Sfeir and {de Lange}, Titia",

year = "2013",

month = feb,

day = "8",

doi = "10.1126/science.1231573",

language = "English",

volume = "339",

pages = "700--4",

journal = "Science",

issn = "0036-8075",

publisher = "AMER ASSOC ADVANCEMENT SCIENCE",

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}

TY - JOUR

T1 - 53BP1 regulates DSB repair using Rif1 to control 5' end resection

AU - Zimmermann, Michal

AU - Lottersberger, Francisca

AU - Buonomo, Sara B

AU - Sfeir, Agnel

AU - de Lange, Titia

PY - 2013/2/8

Y1 - 2013/2/8

N2 - 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.

AB - 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.

KW - animals

KW - BRCA1 protein

KW - cells

KW - chromosomal proteins

KW - DNA

KW - DNA breaks

KW - DNA end-joining repair

KW - DNA repair

KW - DNA-binding proteins

KW - mice

KW - replication protein A

KW - telomere

KW - telomere-binding proteins

KW - telomeric repeat binding protein 2

KW - tumor suppressor p53-binding protein 1

KW - double stranded

KW - non histone

KW - cultured

U2 - 10.1126/science.1231573

DO - 10.1126/science.1231573

M3 - Article

C2 - 23306437

SN - 0036-8075

VL - 339

SP - 700

EP - 704

JO - Science

JF - Science

IS - 6120

ER -

53BP1 regulates DSB repair using Rif1 to control 5' end resection

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

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