The cDNA generated by reverse transcription during retrotransposon and retrovirus replication can enter the genome by two pathways: it can integrate by using the element-encoded integrase or it can recombine with preexisting elements by using the recombination system of the host (6
). Entry into the genome, regardless of the mechanism, alters the host’s genetic material. This can have immediate negative consequences, for example, by generating deleterious mutations. Over evolutionary time, however, some retroelement-induced mutations have likely benefited the host by contributing to the genetic variability that is acted upon by natural selection. In addition, there is increasing evidence that retroelements may contribute to specific cellular processes. The clearest example is the role played by retroelements and reverse transcription in telomere maintenance (24
The evolution of linear chromosomes has presented a particular difficulty for chromosome replication. Chromosome termini become shorter after each round of DNA replication due to the inability to completely replicate chromosome ends. For most organisms, telomerase extends chromosome ends by using telomeric RNA as a template for reverse transcription (5
). A clear link between retrotransposons and telomerases has recently been revealed by the cloning of the telomerase catalytic subunit from Euplotes
, yeast, and humans (26
). Amino acid sequence analysis of the catalytic subunit indicates that it is related to retrotransposon reverse transcriptases. This suggests that during the evolution of linear chromosomes, a reverse transcriptase may have been borrowed from cellular retrotransposons and used to maintain chromosome ends (11
In some instances, retrotransposons play a direct role in counterbalancing the telomeric sequence loss that occurs as a consequence of DNA replication. Drosophila melanogaster
telomeres, for example, are made up of the non-long terminal repeat retrotransposons HeT-A
). Telomere extension occurs through preferential integration of these elements onto chromosome ends (3
). In addition, an increasing number of retroelements have been identified in the telomeric and subtelomeric regions of other species. These include the SART1
elements of silkworms, the Zepp
elements of Chlorella
, and the Ty5 retrotransposons of Saccharomyces
). The presence of these elements at telomeres suggests that they may contribute to telomere maintenance.
Recombination can also compensate for the telomere shortening that results from DNA replication. Amplification of chromosome end sequences can occur through recombination between telomeric or subtelomeric repeats (27
). Recombinational amplification of yeast subtelomeric repeats can overcome telomerase defects and suppress the decreased life span phenotype typically associated with such mutations (30
). This amplification requires the host’s homologous recombination system, namely, the RAD52 gene product.
Our laboratory works on the Ty5 retrotransposons of Saccharomyces
, which integrate preferentially into silent chromatin (54
). Silent chromatin encompasses yeast telomeres and the silent mating loci and is important in mediating Ty5’s target preference (22
). Ty5 can recognize domains of silent chromatin, and a single amino acid change at the border of integrase and reverse transcriptase abolishes target specificity (14
). We have previously shown that in addition to integration, Ty5 cDNA recombines at high frequencies with homologous substrates (20
). In this study, we demonstrate that Ty5 cDNA also recombines preferentially with substrates located in silent chromatin. The preferential amplification of Ty5 at the telomeres through both integration and recombination demonstrates how retrotransposons can contribute to telomere dynamics.