Nickel Stimulates L1 Retrotransposition by a Post-transcriptional Mechanism

Funding Source

National Institutes of Health, National Science Foundation

Grant Number

RO1 GM45668, 1S11ES09996, EPS-034611, DAMD17-02-1-0597, P20 RR020152


Department of Biology

Document Type


Publication Date



Sequence studies of the human genome demonstrate that almost half of the DNA is derived from mobile elements. Most of the current retrotransposition activity arises from L1 and the L1-dependent, non-autonomous elements, such as Alu, contributing to a significant amount of genetic mutation and genomic instability. We present data demonstrating that nickel chloride, but not cobalt chloride, is able to stimulate L1 retrotransposition about 2.5-fold. Our data suggest that the stimulation occurs at a post-transcriptional level, possibly during the integration process. The effect of nickel on the cell is highly complex, limiting the determination of the exact mechanism of this stimulation. The observed stimulation of L1 retrotransposition is not due to a general increase in L1 transcription or an increase in the number of genomic nicks caused by nickel, but more likely caused by a decrease in DNA repair activities that influence the downstream events of retrotransposition. Our observations demonstrate the influence of environmental toxicants on human retroelement activity. We present an additional mechanism for heavy-metal carcinogenesis, where DNA damage through mobile element activation must be considered when dealing with genomic damage/instability in response to environmental agents.


DOI: 10.1016/j.jmb.2005.09.050

PubMed ID: 16249005

Funding text

This research was supported by National Institutes of Environmental and Health Sciences ARCH grant, 1S11ES09996 (to S.P.K. and P.L.D.) NIH RO1 GM45668 (to P.L.D.), NSF EPS-034611 (to P.L.D.), the State of Louisiana Board of Reagents Support Fund (to P.L.D.) and NIH P20 RR020152 (to A.M.R.-E. and P.L.D.), by the Department of the Army (to D.O.D.) breast cancer graduate fellowship (DAMD17-02-1-0597) to V.T.B. and by a student fellowship from the Cancer Association of Greater New Orleans to M.E.-S. We thank Drs Weiping Zou and Erik Flemington for help with the FACS analysis.