Reverse transcriptase at bacterial telomeres.

I n the past two decades, intense efforts have been devoted to uncovering the mechanisms responsible for the maintenance of telomeres in eukaryotic cells. These efforts have led to the identification of an unusual reverse transcriptase (RT), named telomerase, that uses an integral RNA subunit as template to synthesize a short reiterated sequence at the ends of eukaryotic chromosomes (Fig. 1A) (1). In recent years, the study of eukaryotic telomeres and telomerase has received additional attention because of their established roles in cellular senescence and genome stability (2). Although much less commonly appreciated, linear chromosomes and telomeres are not exclusive to the eukaryotic kingdom; they can be found in a number of bacteria, including Streptomyces, Borrelia, Rhodococcus, etc. (3). In contrast to eukaryotic telomeres, the bacterial versions (at least in some cases) consist of multiple inverted repeats (Fig. 1B). Much of the current knowledge on bacterial telomere maintenance is derived from analyses of linear chromosomes and plasmids in Streptomyces spp. Early studies indicate that replication of these plasmids initiates from an internal origin, resulting in the generation of a leading strand 3 overhang, and incomplete duplication of the lagging strand (4). Thus, similar to eukaryotic telomeres, a restorative or compensatory mechanism is required to prevent the loss of genetic information. In a series of elegant papers, Cohen and colleagues (5–7) showed that the ‘‘patching’’ of the 5 -recessed ends of Streptomyces plasmids is likely accomplished through a protein-primed mechanism, in which a protein named Tap recognizes a folded structure generated by the 3 overhang, recruits the Tpg protein, which then serves as primer for the synthesis of DNA on the 5 -recessed strand (Fig. 1B) (5–7). This view of bacterial telomere maintenance would thus not appear to require the participation of an RT. Or would it? In this issue of PNAS, Bao and Cohen (8) describe that the aforementioned Tap protein is, in fact, associated with RTs. They introduced a His6-tagged Tap into Streptomyces, purified it along with associated proteins, and showed that the purified complex bears substantial RT activity. Further analysis revealed that neither Tap nor Tpg was responsible for the activity. Instead, the RT activity copurified with two polypeptides that were in the telomere complex but that can be separately resolved from Tap by additional chromatographic steps. That these two polypeptides have inherent RT activity