@misc{10481/88522,
year = {2019},
url = {https://hdl.handle.net/10481/88522},
abstract = {L1 retrotransposon-derived sequences comprise
approximately 17% of the human genome. Darwinian
selectivepressures alter L1genomicdistributionsduring
evolution, confounding the ability to determine
initial L1 integration preferences. Here, we generated
high-confidence datasets of greater than 88,000 engineered
L1 insertions in human cell lines that act as
proxies for cells that accommodate retrotransposition
in vivo. Comparing these insertions to a null model,
in which L1 endonuclease activity is the sole determinant
dictating L1 integration preferences, demonstrated
that L1 insertions are not significantly enriched
in genes, transcribed regions, or open chromatin. By
comparison, we provide compelling evidence that
the L1 endonuclease disproportionately cleaves predominant
lagging strand DNA replication templates,
while lagging strand 3’-hydroxyl groups may prime
endonuclease-independent L1 retrotransposition in a
Fanconi anemia cell line. Thus, acquisition of an endonucleasedomain,
in conjunctionwith the ability to integrate
into replicating DNA, allowed L1 to become an
autonomous, interspersed retrotransposon.},
organization = {Funding support: D.A.F, NIH
training grant T32 HG000040; M.L., NIH grant UM1 HG009382; J.L.G.P.,
grants MINECO-FEDER (SAF2017-89745-R), the European Research Council
(ERC-Consolidator ERC-STG-2012-309433), and the Howard Hughes Medical
Institute (HHMI; IECS-55007420); T.E.W., NIH grants CA200731 and
GM120767; and J.V.M., NIH grants GM060518 and U01MH106892 and previous
funding from HHMI.},
publisher = {Cell Press},
title = {Genome-wide de novo L1 Retrotransposition Connects Endonuclease Activity with Replication},
doi = {10.1016/j.cell.2019.02.050},
author = {Flasch, Diane A. and Rodríguez Heras, Sara and García Pérez, José Luis},
}