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PMID: 12640136 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

p53 Binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice.

Molecular and cellular biology ·Vol. 23 ·No. 7 ·2003-04-00 ·Pages 2556-63

Ward IM, Minn K, van Deursen J, Chen J

Abstract

53BP1 is a p53 binding protein of unknown function that binds to the central DNA-binding domain of p53. It relocates to the sites of DNA strand breaks in response to DNA damage and is a putative substrate of the ataxia telangiectasia-mutated (ATM) kinase. To study the biological role of 53BP1, we disrupted the 53BP1 gene in the mouse. We show that, similar to ATM(-/-) mice, 53BP1-deficient mice were growth retarded, immune deficient, radiation sensitive, and cancer prone. 53BP1(-/-) cells show a slight S-phase checkpoint defect and prolonged G(2)/M arrest after treatment with ionizing radiation. Moreover, 53BP1(-/-) cells feature a defective DNA damage response with impaired Chk2 activation. These data indicate that 53BP1 acts downstream of ATM and upstream of Chk2 in the DNA damage response pathway and is involved in tumor suppression.

MeSH Terms
Animals Carrier Proteins/genetics,metabolism Cell Cycle/physiology Chromosomal Proteins, Non-Histone DNA Damage/physiology DNA-Binding Proteins Gene Targeting Growth Disorders/complications,genetics Intracellular Signaling Peptides and Proteins Lymphoma/complications,genetics,pathology Mice Mice, Knockout Neoplastic Syndromes, Hereditary/complications,genetics Phenotype Phosphoproteins Protein Binding/physiology Radiation Tolerance/genetics Tumor Suppressor Proteins/metabolism Tumor Suppressor p53-Binding Protein 1
Chemicals
Carrier Proteins Chromosomal Proteins, Non-Histone DNA-Binding Proteins Intracellular Signaling Peptides and Proteins Phosphoproteins Trp53bp1 protein, mouse Tumor Suppressor Proteins Tumor Suppressor p53-Binding Protein 1
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ward Irene M
Department of Oncology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Minn Kay
van Deursen Jan
Chen Junjie
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31 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.23.7.2556-2563.2003
Published
2003-04-00
Pages
2556-63
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC150747
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.23.7.2556-2563.2003 PMC Full Text View journal details
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