In the human genome, the insertion of LINE-1 and Alu elements can affect genes by sequence disruption, and by the introduction of elements that modulate the gene’s expression. One of the modulating sequences retroelements may contribute is the canonical polyadenylation signal (pA), AATAAA. L1 elements include these within their own sequence and AATAAA sequences are commonly created in the A-rich tails of both SINEs and LINEs. Computational analysis of 34 genes randomly retrieved from the human genome draft sequence reveals an orientation bias, reflected as a lower number of L1s and Alus containing the pA in the same orientation as the gene. Experimental studies of Alu-based pA sequences when placed in pol II or pol III transcripts suggest that the signal is very weak, or often not used at all. Because the pA signal is highly affected by the surrounding sequence, it is likely that the Alu constructs evaluated did not provide the required recognition signals to the polyadenylation machinery. Although the effect of pA signals contributed by Alus is individually weak, the observed reduction of “sense” oriented pA-containing L1 and Alu elements within genes reflects that even a modest influence causes a change in evolutionary pressure, sufficient to create the biased distribution.

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.

Repetitive elements comprise over 50% of the mammalian genome, the majority of these being made up of mobile elements. Although most of the mobile elements are inactive, a number are still actively amplifying. This results in a significant level of insertional mutagenesis. Mobile elements contribute even more to aberrant recombination events that produce germ‐line mutations, as well as probably playing a major role in genetic instability in cancer. Other repetitive elements, such as chromosomal duplications and microsatellites (particularly triplet repeats), also lead to genetic damage.