RT Journal
A1 Zingler, Nora
A1 Willhoeft, Ute
A1 Brose, Hans-Peter
A1 Schoder, Volker
A1 Jahns, Thomas
A1 Hanschmann, Kay-Martin O.
A1 Morrish, Tammy A.
A1 Löwer, Johannes
A1 Schumann, Gerald G.
T1 Analysis of 5′ junctions of human LINE-1 and Alu retrotransposons suggests an alternative model for 5′-end attachment requiring microhomology-mediated end-joining
JF Genome Research 
JO Genome Research 
YR 2005 
FD June 01 
VO 15 
IS 6 
SP 780 
OP 789 
DO 10.1101/gr.3421505 
UL http://genome.cshlp.org/content/15/6/780.abstract 
AB Insertion of the human non-LTR retrotransposon LINE-1 (L1) into chromosomal DNA is thought to be initiated by a mechanism called target-primed reverse transcription (TPRT). This mechanism readily accounts for the attachment of the 3′-end of an L1 copy to the genomic target, but the subsequent integration steps leading to the attachment of the 5′-end to the chromosomal DNA are still cause for speculation. By applying bioinformatics to analyze the 5′ junctions of recent L1 insertions in the human genome, we provide evidence that L1 uses at least two distinct mechanisms to link the 5′-end of the nascent L1 copy to its genomic target. While 5′-truncated L1 elements show a statistically significant preference for short patches of overlapping nucleotides between their target site and the point of truncation, full-length insertions display no distinct bias for such microhomologies at their 5′-ends. In a second genome-wide approach, we analyzed Alu elements to examine whether these nonautonomous retrotransposons, which are thought to be mobilized through L1 proteins, show similar characteristics. We found that Alu elements appear to be predominantly integrated via a pathway not involving overlapping nucleotides. The results indicate that a cellular nonhomologous DNA end-joining pathway may resolve intermediates from incomplete L1 retrotransposition events and thus lead to 5′ truncations.