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Molecular and Cellular Biology, February 2009, p. 1050-1058, Vol. 29, No. 4
0270-7306/09/$08.00+0     doi:10.1128/MCB.01011-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

An Oligomerized 53BP1 Tudor Domain Suffices for Recognition of DNA Double-Strand Breaks{triangledown}

Omar Zgheib,1,2 Kristopher Pataky,3 Juergen Brugger,3 and Thanos D. Halazonetis1*

Department of Molecular Biology and Department of Biochemistry, University of Geneva, CH-1205 Geneva, Switzerland,1 Program in Biochemistry, Biomedical Graduate Studies, University of Pennsylvania, Philadelphia, Pennsylvania 19104,2 Microsystems Laboratory, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland3

Received 27 June 2008/ Returned for modification 12 August 2008/ Accepted 26 November 2008

53BP1, the vertebrate ortholog of the budding yeast Rad9 and fission yeast Crb2/Rhp9 checkpoint proteins, is recruited rapidly to sites of DNA double-strand breaks (DSBs). A tandem tudor domain in human 53BP1 that recognizes methylated residues in the histone core is necessary, but not sufficient, for efficient recruitment. By analysis of deletion mutants, we identify here additional elements in 53BP1 that facilitate recognition of DNA DSBs. The first element corresponds to an independently folding oligomerization domain. Replacement of this domain with heterologous tetramerization domains preserves the ability of 53BP1 to recognize DNA DSBs. A second element is only about 15 amino acids long and appears to be a C-terminal extension of the tudor domain, rather than an independently functioning domain. Recruitment of 53BP1 to sites of DNA DSBs is facilitated by histone H2AX phosphorylation and ubiquitination. However, none of the 53BP1 domains/elements important for recruitment are known to bind phosphopeptides or ubiquitin, suggesting that histone phosphorylation and ubiquitination regulate 53BP1 recruitment to sites of DNA DSBs indirectly.

* Corresponding author. Mailing address: Department of Molecular Biology, University of Geneva, Sciences III, 30, quai Ernest-Ansermet, CH-1205 Geneva, Switzerland. Phone: (41) 22-379-6112. Fax: (41) 22-379-6868. E-mail: thanos.halazonetis{at}unige.ch

{triangledown} Published ahead of print on 8 December 2008.

Molecular and Cellular Biology, February 2009, p. 1050-1058, Vol. 29, No. 4
0270-7306/09/$08.00+0     doi:10.1128/MCB.01011-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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