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Retrotransposon Suicide: Formation of Ty1 Circles and Autointegration via a Central DNA Flap ^,

Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, Frederick, Maryland 21702-1201,¹ HIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland 21702-1201²

Received 12 July 2006/ Accepted 23 September 2006

Despite their evolutionary distance, the Saccharomyces cerevisiae retrotransposon Ty1 and retroviruses use similar strategies for replication, integration, and interactions with their hosts. Here we examine the formation of circular Ty1 DNA, which is comparable to the dead-end circular products that arise during retroviral infection. Appreciable levels of circular Ty1 DNA are present with one-long terminal repeat (LTR) circles and deleted circles comprising major classes, while two-LTR circles are enriched when integration is defective. One-LTR circles persist when homologous recombination pathways are blocked by mutation, suggesting that they result from reverse transcription. Ty1 autointegration events readily occur, and many are coincident with and dependent upon DNA flap structures that result from DNA synthesis initiated at the central polypurine tract. These results suggest that Ty1-specific mechanisms minimize copy number and raise the possibility that special DNA structures are a targeting determinant.

Published ahead of print on 27 September 2006.

Supplemental material for this article may be found at http://jvi.asm.org/.

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