Abstract
VDJ recombination: Artemis and its in vivo role in hairpin opening.
Highlights
Artemis is the newest player in VDJ recombination and double strand break repair
VDJ recombination is directed to the immunoglobulin and TCR loci by highly conserved recombination signal sequences (RSSs) comprised of a heptamer and a nonamer motif with an intervening 12- or 23-bp spacer
During the initial stages of the reaction, RAG-1/RAG-2 form a complex with the RSS, which is in part stabilized by the interactions between the nonamer binding domain of RAG-1 and the nonamer motif
Summary
Artemis is the newest player in VDJ recombination and double strand break repair. First identified in radiationsensitive and immune-deficient patients, it was recently shown to interact with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and have nuclease activity, becoming the most popular candidate for the opening of hairpin coding ends. In vitro experiments demonstrated that after RSS cleavage, RAG-1/RAG-2 and HMG1 proteins remain bound in a complex with the resulting 5Ј phosphorylated blunt signal end and the hairpin coding end in what is known as the postcleavage complex [7]. Evidence supporting the participation of these protein complexes in hairpin coding end opening and processing will be further discussed.
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