Telomeres: No end in sight

Abstract

Why do eukaryotic chromosomes end the way they do? One basic function of teiomeres, the ends of chromosomes, is to preserve themselves; they allow replenishment of the chromosomai DNA termini by an independent mechanism of DNA synthesis, to make up for the incomplete replication of the 5’ end of each chromosomal DNA strand by the primary cellular DNA replication machinery. But why is a special DNA sequence needed at teiomeres? Obsetvations of teiomere behavior indicate that teiomeres play multiple roles, some new and surprising. This minireview highlights recent work that throws into sharp relief the question of why a specific DNA sequence is required to stabilize chromosomes. The Correct Telomeric DNA Sequence Is Necessary to Stabilize Chromosomes In a great phyiogenetic variety of eukaryotes, teiomeric DNA consists of a terminal stretch of tandem, speciesspecific repeats of very short (typically 5-8 bp) simple sequences, characterized by clusters of G residues on the strand that forms the 3’ end of each chromosomai DNA strand. This strand is synthesized by the ribonucieoprotein enzyme telomerase (reviewed by Blackburn, 1992) an essential cellular reverse transcriptase that uses a short sequence within its RNA moiety as the template for addition of the G-cluster teiomeric DNA strand to chromosome ends. Without replenishment of telomeric sequences, which normally requires telomerase to make up for losses caused by incomplete replication, the chromosome ends gradually recede (Figure 1). Usually, chromosomes with broken ends lacking their species-specific teiomeric DNA sequences or that fail to maintain preexisting teiomeric DNA on the end of chromosomes are not stably maintained (reviewed by Blackburn, 1991). This instability has been emphasized by recent studies in the yeast Saccharomyces cerevisiae. Sandeil and Zakian (1993) removed a telomere in a controlled way from a dispensable chromosome and watched the fate of the chromosome immediately thereafter. The short-term response of the ceil was very similar to that elicited by introducing a single break into a circular, nonessential plasmid, producing two teiomereiess ends; this response included temporary arrest of the ceil cycle (Bennett et al., 1993; Sandeii and Zakian, 1993). Subsequently, the linear chromosome lacking one teiomere was lost, although sometimes only after several ceil divisions, unless it was stabilized by acquiring ateiomere by some means (Sandeii and Zakian, 1993). Another line of evidence highlighting the need for the telomeric DNA sequence itself to maintain chromosomes stably in yeast has come from asking how cells can survive Minireview