LINE-1 retrotransposition and its deregulation in cancers: implications for therapeutic opportunities
- 1Department of Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA;
- 2Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 3Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA
- Corresponding authors: kathleenh_burns{at}dfci.harvard.edu, carlos_mendez-dorantes{at}dfci.harvard.edu
Abstract
Long interspersed element 1 (LINE-1) is the only protein-coding transposon that is active in humans. LINE-1 propagates in the genome using RNA intermediates via retrotransposition. This activity has resulted in LINE-1 sequences occupying approximately one-fifth of our genome. Although most copies of LINE-1 are immobile, ∼100 copies are retrotransposition-competent. Retrotransposition is normally limited via epigenetic silencing, DNA repair, and other host defense mechanisms. In contrast, LINE-1 overexpression and retrotransposition are hallmarks of cancers. Here, we review mechanisms of LINE-1 regulation and how LINE-1 may promote genetic heterogeneity in tumors. Finally, we discuss therapeutic strategies to exploit LINE-1 biology in cancers.
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Footnotes
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.351051.123.
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Freely available online through the Genes & Development Open Access Option.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
