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Published in: Cancer Cell International 1/2006

Open Access 01-12-2006 | Primary research

Human LINE-1 retrotransposon induces DNA damage and apoptosis in cancer cells

Authors: S Mehdi Belgnaoui, Roger G Gosden, O John Semmes, Abdelali Haoudi

Published in: Cancer Cell International | Issue 1/2006

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Abstract

Background

Long interspersed nuclear elements (LINEs), Alu and endogenous retroviruses (ERVs) make up some 45% of human DNA. LINE-1 also called L1, is the most common family of non-LTR retrotransposons in the human genome and comprises about 17% of the genome. L1 elements require the integration into chromosomal target sites using L1-encoded endonuclease which creates staggering DNA breaks allowing the newly transposed L1 copies to integrate into the genome. L1 expression and retrotransposition in cancer cells might cause transcriptional deregulation, insertional mutations, DNA breaks, and an increased frequency of recombinations, contributing to genome instability. There is however little evidence on the mechanism of L1-induced genetic instability and its impact on cancer cell growth and proliferation.

Results

We report that L1 has genome-destabilizing effects indicated by an accumulation of γ-H2AX foci, an early response to DNA strand breaks, in association with an abnormal cell cycle progression through a G2/M accumulation and an induction of apoptosis in breast cancer cells. In addition, we found that adjuvant L1 activation may lead to supra-additive killing when combined with radiation by enhancing the radiation lethality through induction of apoptosis that we have detected through Bax activation.

Conclusion

L1 retrotransposition is sensed as a DNA damaging event through the creation DNA breaks involving L1-encoded endonuclease. The apparent synergistic interaction between L1 activation and radiation can further be utilized for targeted induction of cancer cell death. Thus, the role of retrotransoposons in general, and of L1 in particular, in DNA damage and repair assumes larger significance both for the understanding of mutagenicity and, potentially, for the control of cell proliferation and apoptosis.
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Metadata
Title
Human LINE-1 retrotransposon induces DNA damage and apoptosis in cancer cells
Authors
S Mehdi Belgnaoui
Roger G Gosden
O John Semmes
Abdelali Haoudi
Publication date
01-12-2006
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2006
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-6-13

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