Title

Nucleoside Analogue Reverse Transcriptase Inhibitors Differentially Inhibit Human LINE-1 Retrotransposition

SMC Author

Keith Garrison

SMC Affiliated Work

1

Status

Faculty

School

School of Science

Department

Biology

Document Type

Article

Publication Date

2-2008

Publication Title

PLoS One

Description/Abstract

Background

Intact LINE-1 elements are the only retrotransposons encoded by the human genome known to be capable of autonomous replication. Numerous cases of genetic disease have been traced to gene disruptions caused by LINE-1 retrotransposition events in germ-line cells. In addition, genomic instability resulting from LINE-1 retrotransposition in somatic cells has been proposed as a contributing factor to oncogenesis and to cancer progression. LINE-1 element activity may also play a role in normal physiology.

Methods and Principal Findings

Using an in vitro LINE-1 retrotransposition reporter assay, we evaluated the abilities of several antiretroviral compounds to inhibit LINE-1 retrotransposition. The nucleoside analogue reverse transcriptase inhibitors (nRTIs): stavudine, zidovudine, tenofovir disoproxil fumarate, and lamivudine all inhibited LINE-1 retrotransposition with varying degrees of potencies, while the non-nucleoside HIV-1 reverse transcriptase inhibitor nevirapine showed no effect.

Conclusions/Significance

Our data demonstrates the ability for nRTIs to suppress LINE-1 retrotransposition. This is immediately applicable to studies aimed at examining potential roles for LINE-1 retrotransposition in physiological processes. In addition, our data raises novel safety considerations for nRTIs based on their potential to disrupt physiological processes involving LINE-1 retrotransposition.

Keywords

HIV-1, Human genomics, Physiological processes, Reverse transcription, Enzyme inhibitors, Reverse transcriptase inhibitors, Gene disruption, Nucleosides

Scholarly

yes

Peer Reviewed

1

DOI

10.1371/journal.pone.0001547

Volume

3

Issue

2

First Page

e1547

Disciplines

Biology

Original Citation

Jones RB, Garrison KE, Wong JC, Duan EH, Nixon DF, Ostrowski MA. 2008. Nucleoside Analogue Reverse Transcriptase Inhibitors Differentially Inhibit Human LINE-1 Retrotransposition. PLoS One 3 (2): e1547.

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