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Molecular and Cellular Biology, April 2003, p. 2556-2563, Vol. 23, No. 7
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.7.2556-2563.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

p53 Binding Protein 53BP1 Is Required for DNA Damage Responses and Tumor Suppression in Mice

Irene M. Ward,1 Kay Minn,1 Jan van Deursen,2 and Junjie Chen1*

Departments of Oncology,1 Pediatric and Adolescent Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 559052

Received 19 November 2002/ Returned for modification 14 December 2002/ Accepted 7 January 2003

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 G2/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.

* Corresponding author. Mailing address: Department of Oncology, Mayo Clinic and Foundation, Rm. 1306, Guggenheim Bldg., 200 First St., SW, Rochester, MN 55905. Phone: (507) 538-1545. Fax: (507) 284-3906. E-mail: chen.junjie{at}mayo.edu.

Molecular and Cellular Biology, April 2003, p. 2556-2563, Vol. 23, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.7.2556-2563.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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