Endonuclease-independent LINE-1 retrotransposition at mammalian telomeres
dc.contributor.author | Morrish, Tammy A. | en_US |
dc.contributor.author | Garcia-Perez, Jose Luis | en_US |
dc.contributor.author | Stamato, Thomas D. | en_US |
dc.contributor.author | Taccioli, Guillermo E. | en_US |
dc.contributor.author | Sekiguchi, Jo Ann | en_US |
dc.contributor.author | Moran, John V. | en_US |
dc.date.accessioned | 2009-06-01T17:47:11Z | |
dc.date.available | 2009-06-01T17:47:11Z | |
dc.date.issued | 2007-03-08 | en_US |
dc.identifier.citation | Morrish, Tammy A.; Garcia-Perez, Jose Luis; Stamato, Thomas D.; Taccioli, Guillermo E.; Sekiguchi, JoAnn; Moran, John V.. (2007) "Endonuclease-independent LINE-1 retrotransposition at mammalian telomeres." Nature 446(7132): 208-212. <http://hdl.handle.net/2027.42/62964> | en_US |
dc.identifier.issn | 0028-0836 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/62964 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=17344853&dopt=citation | en_US |
dc.description.abstract | Long interspersed element-1 (LINE-1 or L1) elements are abundant, non-long-terminal-repeat (non-LTR) retrotransposons that comprise 17% of human DNA(1). The average human genome contains similar to 80-100 retrotransposition- competent L1s (ref. 2), and they mobilize by a process that uses both the L1 endonuclease and reverse transcriptase, termed target-site primed reverse transcription(3-5). We have previously reported an efficient, endonuclease-independent L1 retrotransposition pathway (ENi) in certain Chinese hamster ovary (CHO) cell lines that are defective in the non-homologous end-joining (NHEJ) pathway of DNA double-strand-break repair(6). Here we have characterized ENi retrotransposition events generated in V3 CHO cells, which are deficient in DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity and have both dysfunctional telomeres and an NHEJ defect. Notably, similar to 30% of ENi retrotransposition events insert in an orientation-specific manner adjacent to a perfect telomere repeat (5'-TTAGGG-3'). Similar insertions were not detected among ENi retrotransposition events generated in controls or in XR-1 CHO cells deficient for XRCC4, an NHEJ factor that is required for DNA ligation but has no known function in telomere maintenance. Furthermore, transient expression of a dominant-negative allele of human TRF2 ( also called TERF2) in XRCC4-deficient XR-1 cells, which disrupts telomere capping, enables telomere-associated ENi retrotransposition events. These data indicate that L1s containing a disabled endonuclease can use dysfunctional telomeres as an integration substrate. The findings highlight similarities between the mechanism of ENi retrotransposition and the action of telomerase, because both processes can use a 3' OH for priming reverse transcription at either internal DNA lesions or chromosome ends(7,8). Thus, we propose that ENi retrotransposition is an ancestral mechanism of RNA-mediated DNA repair associated with non-LTR retrotransposons that may have been used before the acquisition of an endonuclease domain. | en_US |
dc.format.extent | 762250 bytes | |
dc.format.extent | 2489 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Nature Publishing Group | en_US |
dc.source | Nature | en_US |
dc.title | Endonuclease-independent LINE-1 retrotransposition at mammalian telomeres | en_US |
dc.type | Article | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationum | Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA | en_US |
dc.contributor.affiliationother | Lankenau Inst Med Res, Wynnewood, PA 19096 USA | en_US |
dc.contributor.affiliationother | Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA | en_US |
dc.identifier.pmid | 17344853 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/62964/1/nature05560.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1038/nature05560 | en_US |
dc.identifier.source | Nature | en_US |
dc.contributor.authoremail | morrisht@jhmi.edu; moranj@umich.edu | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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