8 Telomerase-independent Telomere Maintenance in Yeast

Abstract

Prior to identification of telomerase, recombination was considered a possible mechanism for telomere maintenance (see Chapter 1). Although normal telomeres are generally thought to be refractory to recombination, homologous recombination can provide a mechanism for telomere maintenance when telomerase is absent and telomeres become progressively shorter. Here, we review the mechanisms of telomerase-independent telomere maintenance in budding yeasts with particular emphasis on Saccharomyces cerevisiae and Kluyveromyces lactis. Other chapters in this book discuss telomerase-independent telomere maintenance in fission yeast, mammals, and Drosophila. Work on S. cerevisiae has revealed two major recombination-based pathways that produce rare survivors among senescent cells lacking telomerase. These two RAD52-dependent pathways differ in the sequences they add to chromosome ends and in the proteins that participate in the elongation process. Both pathways appear to be closely related to break-induced replication (BIR), a recombination pathway that can repair chromosomal double-strand breaks (DSBs). In addition, an alternative, apparently recombination-independent pathway has been described in which chromosome ends are maintained without any canonical telomeric sequences. Work on K. lactis has provided additional insights concerning recombinational telomere elongation (RTE), suggesting a major role for rolling-circle replication between shortened telomere ends and extrachromosomal telomeric circles, followed by recombination-mediated spreading of sequences from one telomere to all others.

RECOMBINATION-MEDIATED TELOMERE MAINTENANCE IN S. CEREVISIAE
Telomeres in S. cerevisiae and K. lactis are normally a few hundred base pairs in length and shorten at rates of 3–5 bp per cell division in the absence of telomerase. Mutants missing one or more of...