The telomeric retrotransposons in Drosophila are activated and replicated at the G1/S boundary. Liang Zhang, Yikang Rong. National Cancer Institute, Bethesda, MD.

   In place of telomerase, Drosophila species have tamed a group of retrotransposons that transpose exclusively and repeatedly to chromosome ends to buffer the loss of chromosome end sequences during DNA replication. To better understand how the retrotransposons co-operate with the host cellular machinery to accomplish the end-elongation function, we characterized Het-A, the most abundant telomeric element in Drosophila melanogaster. The single open reading frame of HeT-A encodes a 110kD protein (ORF1p). We showed that in a narrow window during the cell cycle, Het-A sense transcript and ORF1p forms RNP complexes that are targeted to telomeres. Furthermore, Verrochio, a protein homologous to conserved Stn1 protein with a potential role in the maintenance of telomeric single stranded overhangs, is a key regulator of this end-targeting process. Using cytological markers for different phases of the cell cycle in Orf1p co-immunolocalization experiments, we revealed that Het-A RNPs are only present during late G1 to early S phase. By analyzing the behavior of a single telomere that is marked with a lacO array, we discovered that HeT-A RNP is often associated with a telomere undergoing DNA replication. Our results have served as the first evidence that Drosophila telomeres are likely among the first genomic regions replicated during the S phase, and these findings have implications for the underlying mechanism that leads to the exclusive targeting of these retro-elements to the chromosome ends.