Role of poly(ADP-ribosyl)ation in DNA-PKcs-independent V(D)J recombination

Matthew L. Brown, Daniel Franco, Alexander Bürkle, Yung Chang

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

V(D)J recombination is critical to the generation of a functional immune system. Intrinsic to the assembly of antigen receptor genes is the formation of endogenous DNA double-strand breaks, which normally are excluded from the cellular surveillance machinery because of their sequestration in a synaptic complex and/or rapid resolution. In cells deficient in double-strand break repair, such recombination-induced breaks fail to be joined promptly and therefore are at risk of being recognized as DNA damage. Poly(ADP-ribose) polymerase-1 is an important factor in the maintenance of genomic integrity and is believed to play a central role in DNA repair. Here we provide visual evidence that in a recombination inducible severe combined immunodeficient cell line poly-(ADP-ribose) formation occurs during the resolution stage of V(D)J recombination where nascent opened coding ends are generated. Poly(ADP-ribose) formation appears to facilitate coding end resolution. Furthermore, formation of Mre11 foci coincide with these areas of poly(ADP-ribosyl)ation. In contrast, such a response is not observed in wild-type cells possessing a functional catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). Thus, V(D)J recombination invokes a DNA damage response in cells lacking DNA-PKcs activity, which in turn promotes DNA-PKcs-independent resolution of recombination intermediates.

Original languageEnglish (US)
Pages (from-to)4532-4537
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number7
DOIs
Publication statusPublished - Apr 2 2002

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ASJC Scopus subject areas

  • Genetics
  • General

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