53BP1 Enforces Distinct Pre- and Post-resection Blocks on Homologous Recombination.

Aging / drug effects Animals BRCA1 Protein / genetics DNA Breaks, Double-Stranded / drug effects DNA Damage / drug effects Genomic Instability / drug effects Homologous Recombination / drug effects Mice Mutation / drug effects Poly(ADP-ribose) Polymerase Inhibitors / pharmacology Rad51 Recombinase / genetics Tumor Suppressor p53-Binding Protein 1 / genetics Ubiquitin-Protein Ligases / genetics
53BP1 BRCA1 PARPi aging cancer homologous recombination resection shieldin

Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
02 01 2020
Historique:
received: 24 06 2019
revised: 17 08 2019
accepted: 20 09 2019
pubmed: 28 10 2019
medline: 28 3 2020
entrez: 27 10 2019
Statut: ppublish

Résumé

53BP1 activity drives genome instability and lethality in BRCA1-deficient mice by inhibiting homologous recombination (HR). The anti-recombinogenic functions of 53BP1 require phosphorylation-dependent interactions with PTIP and RIF1/shieldin effector complexes. While RIF1/shieldin blocks 5'-3' nucleolytic processing of DNA ends, it remains unclear how PTIP antagonizes HR. Here, we show that mutation of the PTIP interaction site in 53BP1 (S25A) allows sufficient DNA2-dependent end resection to rescue the lethality of BRCA1

Identifiants

DOI: 10.1016/j.molcel.2019.09.024 PMID: 31653568 PMC: PMC6993210
pubmed: 31653568
pii: S1097-2765(19)30729-4
doi: 10.1016/j.molcel.2019.09.024
pmc: PMC6993210
mid: NIHMS1543692
pii:
doi:

Substances chimiques

BRCA1 Protein 0
Poly(ADP-ribose) Polymerase Inhibitors 0
Tumor Suppressor p53-Binding Protein 1 0
Ubiquitin-Protein Ligases EC 2.3.2.27
Rad51 Recombinase EC 2.7.7.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

26-38.e7

Subventions

Organisme : Intramural NIH HHS
ID : Z01 BC010283-10
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 BC010959
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 BC010283
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA033572
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227001
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS037956
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA197506
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

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Auteurs

Elsa Callen (E)

Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Dali Zong (D)

Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Wei Wu (W)

Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Nancy Wong (N)

Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Andre Stanlie (A)

Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Momoko Ishikawa (M)

Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Raphael Pavani (R)

Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Lavinia C Dumitrache (LC)

Department of Genetics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Andrea K Byrum (AK)

Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO 63110, USA.

Carlos Mendez-Dorantes (C)

Department of Cancer Genetics and Epigenetics, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.

Paula Martinez (P)

Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid 28029, Spain.

Andres Canela (A)

Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Yaakov Maman (Y)

Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Amanda Day (A)

Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Michael J Kruhlak (MJ)

Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Maria A Blasco (MA)

Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center, Madrid 28029, Spain.

Jeremy M Stark (JM)

Department of Cancer Genetics and Epigenetics, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.

Nima Mosammaparast (N)

Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO 63110, USA.

Peter J McKinnon (PJ)

Department of Genetics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

André Nussenzweig (A)

Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: andre_nussenzweig@nih.gov.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › 53BP1 Enforces Distinct Pre- and...
questionsmedicales.fr › Eucaryotes › Animaux › 53BP1 Enforces Distinct Pre- and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéine BRCA1 › 53BP1 Enforces Distinct Pre- and...
questionsmedicales.fr › Phénomènes génétiques › Altération de l'ADN › Cassures de l'ADN › Cassures double-brin de l'ADN › 53BP1 Enforces Distinct Pre- and...
questionsmedicales.fr › Phénomènes génétiques › Altération de l'ADN › 53BP1 Enforces Distinct Pre- and...
questionsmedicales.fr › Phénomènes génétiques › Instabilité du génome › 53BP1 Enforces Distinct Pre- and...
questionsmedicales.fr › Phénomènes génétiques › Recombinaison génétique › Recombinaison homologue › 53BP1 Enforces Distinct Pre- and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › 53BP1 Enforces Distinct Pre- and...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › 53BP1 Enforces Distinct Pre- and...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Inhibiteurs de poly(ADP-ribose) polymérases › 53BP1 Enforces Distinct Pre- and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines des groupes de complémentation de l'anémie de Fanconi › Rad51 Recombinase › 53BP1 Enforces Distinct Pre- and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines chromosomiques nonhistones › Protéine-1 liant le suppresseur de tumeur p53 › 53BP1 Enforces Distinct Pre- and...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Ubiquitin-protein ligase complexes › Ubiquitin-protein ligases › 53BP1 Enforces Distinct Pre- and...