53BP1 facilitates long-range DNA end-joining during V(D)J recombination

Simone Difilippantonio, Eric Gapud, Nancy Wong, Ching-Yu Huang, Grace Mahowald, Hua Tang Chen, Michael J. Kruhlak, Elsa Callen, Ferenc Livak, Michel C. Nussenzweig, Barry P. Sleckman and André Nussenzweig ()
Additional contact information
Simone Difilippantonio: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1360, USA
Eric Gapud: Washington University School of Medicine, St Louis, Missouri 63110, USA
Nancy Wong: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1360, USA
Ching-Yu Huang: Washington University School of Medicine, St Louis, Missouri 63110, USA
Grace Mahowald: Washington University School of Medicine, St Louis, Missouri 63110, USA
Hua Tang Chen: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1360, USA
Michael J. Kruhlak: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1360, USA
Elsa Callen: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1360, USA
Ferenc Livak: University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
Michel C. Nussenzweig: Laboratory of Molecular Immunology, The Rockefeller University and Howard Hughes Medical Institute, New York, New York 10021, USA
Barry P. Sleckman: Washington University School of Medicine, St Louis, Missouri 63110, USA
André Nussenzweig: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1360, USA

Nature, 2008, vol. 456, issue 7221, 529-533

Abstract: DNA repair: 53BP1 puts ends in motion When either exogenous or endogenous double-strand breaks occur, the p53 binding protein 53BP1 is one of the earliest proteins to be recruited to the site of the break. 53BP1 helps to promote rejoining of DNA ends during class switch recombination; in a pair of papers in this week's Nature, the laboratories of André Nussenzweig and Titia de Lange show it is also required for V(D)J recombination and for joining of DNA breaks in telomeres. In V(D)J recombination, the ends of the programmed double-strand break are degraded when 53BP1 is absent, and joining between distal V and DJ segments is affected. At broken telomeres, 53BP1 increases the volume of the nucleus searched by the DNA ends so that they are more likely to encounter a partner to which they can be ligated. Thus, 53BP1 facilitates repair by changing the dynamics of movement of broken ends, making long-range interactions more frequent.

Date: 2008
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DOI: 10.1038/nature07476

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