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Lookup NU author(s): Professor Alexander Burkle
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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.
Author(s): Brown ML, Franco D, Burkle A, Chang Y
Publication type: Article
Publication status: Published
Journal: Proceedings of the National Academy of Sciences
Year: 2002
Volume: 99
Issue: 7
Pages: 4532-4537
ISSN (print): 0027-8424
ISSN (electronic):
Publisher: National Academy of Sciences
URL: http://dx.doi.org/10.1073/pnas.072495299
DOI: 10.1073/pnas.072495299
PubMed id: 11930007
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