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Summary: TheJournalofExperimentalMedicine
ARTICLE
The Rockefeller University Press $30.00
J. Exp. Med. Vol. 205 No. 13 3079-3090
www.jem.org/cgi/doi/10.1084/jem.20082271
3079
Ig heavy (IgH) and light (IgL) chain variable
region exons are assembled from component
V, D, and J segments in developing B lympho-
cytes. V(D)J recombination is initiated by the
RAG1/2 endonuclease, which introduces
DNA double-strand breaks (DSBs) between
V, D, and J segments and flanking recombina-
tion signal sequences (RSs) (1). Subsequently,
cleaved coding segments are joined to form
V(D)J exons and RSs are joined to form RS
joins (2). Both coding and RS joining are per-
formed by classical nonhomologous end-join-
ing (C-NHEJ), which is a major general DSB
repair pathway in mammalian cells (3). Xrcc4
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