Twin priming: A proposed mechanism for the creation of inversions in L1 retrotransposition

E. M. Ostertag, Jr Kazazian

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2059-2065
Number of pages7
JournalGenome research
Volume11
Issue number12
DOIs
StatePublished - Dec 27 2001
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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