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Cell Divisions Are Required for L1 Retrotransposition

Department of Biology, University of Rochester, Rochester, New York 14627-0211

Received 5 October 2006/ Returned for modification 7 November 2006/ Accepted 27 November 2007

LINE-1 (L1) retrotransposons comprise a large fraction of genomic DNAs of many organisms. Many L1 elements are active and may generate potentially deleterious mutations by inserting into genes, yet little is known about the control of retrotransposition by the host. Here we examined whether retrotransposition depends on the cell cycle by using a retrotransposition assay with cultured human cells. We show that in both cancer cells and primary human fibroblasts, retrotransposition was strongly inhibited in the cells arrested in the G₁, S, G₂, or M stage of the cell cycle. Retrotransposition was also inhibited during cellular senescence in primary human fibroblasts. The levels of L1 transcripts were strongly reduced in arrested cells, suggesting that the reduction in L1 transcript abundance limits retrotransposition in nondividing cells. We hypothesize that inhibition of retrotransposition in nondividing cells protects somatic tissues from accumulation of deleterious mutations caused by L1 elements.

Published ahead of print on 4 December 2006.

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