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

Irene M. Ward, Kay Minn, Jan Van Deursen, Junjie Chen

Research output: Contribution to journalArticle

291 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)2556-2563
Number of pages8
JournalMolecular and cellular biology
Volume23
Issue number7
DOIs
StatePublished - Apr 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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