Journal
PLOS BIOLOGY
Volume 4, Issue 11, Pages 1934-1946Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.0040350
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Funding
- NIAID NIH HHS [R01 AI036420, AI36420] Funding Source: Medline
- NIEHS NIH HHS [R01 ES005508, ES05508] Funding Source: Medline
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Antigen receptor gene rearrangements are initiated by the RAG1/2 protein complex, which recognizes specific DNA sequences termed RSS ( recombination signal sequences). The RAG recombinase can also catalyze transposition: integration of a DNA segment bounded by RSS into an unrelated DNA target. For reasons that remain poorly understood, such events occur readily in vitro, but are rarely detected in vivo. Previous work showed that non-B DNA structures, particularly hairpins, stimulate transposition. Here we show that the sequence of the four nucleotides at a hairpin tip modulates transposition efficiency over a surprisingly wide ( > 100-fold) range. Some hairpin targets stimulate extraordinarily efficient transposition ( up to 15%); one serves as a potent and specific transposition inhibitor, blocking capture of targets and destabilizing preformed target capture complexes. These findings suggest novel regulatory possibilities and may provide insight into the activities of other transposases.
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