Life and Cancer Without Telomerase

replication, ‫5ف‬ bp per end per cell division, demonstrating that in Drosophila telomeric DNA is not neces-Department of Molecular Biology sary to protect an end from degradation (see for exam-without telomeric DNA appear to function normally, there is no deleterious consequence to the organism until the slow erosion due to incomplete replication Telomeres, the physical ends of eukaryotic chromo-reaches an important gene. In contrast, yeast chromosomes , have until recently been studied almost exclu-somes without telomeres are lost at very high rates (San-sively in model systems. However, within the past few dell and Zakian, 1993), apparently because, yeast ends years, there have been a large number of papers sug-without telomeric DNA are degraded relatively rapidly. gesting that telomere length regulation is important for Nonetheless, even in yeast, a chromosome lacking a aging and tumorigenesis in humans, results that have telomere can be replicated, segregated, and transcribed heightened interest in these fascinating structures. In for as many as ten cell divisions before it is lost. this issue of Cell, Blasco et al. (1997) report the isolation Genes encoding telomerase RNA and, much more of mice with mutations in a gene involved in synthesizing recently, the presumed catalytic protein subunit of telo-telomeric DNA. The phenotypes of these animals pro-merase (Lingner et al., 1997; Meyerson et al., 1997; Naka-vide insight into the importance of mammalian telo-mura et al., 1997) have been identified in several organ-meres for both chromosome stability and cancer. isms. In the yeasts Saccharomyces and Kluyveromyces, Conventional DNA polymerases can not start DNA syn-cells lacking telomerase components lose telomeric thesis de novo and can replicate DNA only in the 5Ј-to-3Ј DNA at the slow rate expected for incomplete replication direction. The replication of eukaryotic chromosomal (Lundblad and Szostak, 1989; McEachern and Blackburn, DNA molecules is typically primed by an 8-to 12-base 1995). Even though these organisms have relatively short stretch of RNA (Figure 1). This mechanism suffices for telomeres, on the order of ‫005–003ف‬ bp, there are no all but the very ends of the chromosome. Removal of major phenotypic consequences of telomerase loss for the terminal RNA primer is expected to generate a small ‫05ف‬ generations. In Saccharomyces, chromosome stabil-gap at the 5Ј ends of newly replicated strands that can ity and cell viability eventually decrease in cells lacking not be repaired by a conventional DNA polymerase. Hence, in the absence of a specialized replication mechanism , a chromosome end …