Nickel stimulates L1 retrotransposition by a post-transcriptional mechanism.
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.
El-Sawy
Mohammed
M
Tulane Cancer Center SL-66, Department of Environmental Health Sciences, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Kale
Shubha P
SP
Dugan
Christine
C
Nguyen
Thuc Quyen
TQ
Belancio
Victoria
V
Bruch
Heather
H
Roy-Engel
Astrid M
AM
Deininger
Prescott L
PL
D002453:Cell Cycle / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008274:Magnesium / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D012333:RNA, Messenger; D003035:Cobalt; C022838:nickel chloride; D009532:Nickel; C018021:cobaltous chloride; D008274:Magnesium