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Vol. 11, Issue 12, 2059-2065, December 2001

LETTER
Twin Priming: A Proposed Mechanism for the Creation of Inversions in L1 Retrotransposition

Eric M. Ostertag, and Haig H. Kazazian Jr.1

Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA

L1 retrotransposons are pervasive in the human genome. Approximately 25% of recent L1 insertions in the genome are inverted and truncated at the 5' end of the element, but the mechanism of L1 inversion has been a complete mystery. We analyzed recent L1 inversions from the genomic database and discovered several findings that suggested a mechanism for the creation of L1 inversions, which we call twin priming. Twin priming is a consequence of target primed reverse transcription (TPRT), a coupled reverse transcription/integration reaction that L1 elements are thought to use during their retrotransposition. In TPRT, the L1 endonuclease cleaves DNA at its target site to produce a double-strand break with two single-strand overhangs. During twin priming, one of the overhangs anneals to the poly(A) tail of the L1 RNA, and the other overhang anneals internally on the RNA. The overhangs then serve as primers for reverse transcription. The data further indicate that a process identical to microhomology-driven single-strand annealing resolves L1 inversion intermediates.

1 Corresponding author.

11:2059-2065 ©2001 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/01 $5.00
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