Telomere maintenance without telomerase

Abstract

Recombination-dependent maintenance of telomeres, ®rst discovered in budding yeast, has revealed an alternative pathway for telomere maintenance that does not require the enzyme telomerase. Experiments conducted in two budding yeasts, S. cerevisiae and K. lactis, have shown recombination can replenish terminal G-rich telomeric tracts that would otherwise shorten in the absence of telomerase, as well as disperse and amplify sub-telomeric repeat elements. Investigation of the genetic requirements for this process have revealed that at least two di erent recombination pathways, de®ned by RAD50 and RAD51, can promote telomere maintenance. Although critically short telomeres are very recombinogenic, recombination among telomeres that have only partially shortened in the absence of telomerase can also contribute to telomerase-independent survival. These observations provide new insights into the mechanism(s) by which recombination can restore telomere function in yeast, and suggest future experiments for the investigation of potentially similar pathways in human cells.

Telomerase core components protect Candida telomeres from aberrant overhang accumulation

“…3B). Both events were likely to reflect the emergence of ''survivors,'' and the distinct kinetics testifies to the stochastic nature of this recombinational process (31,32). In addition, we observed relatively stable telomere maintenance in a ter1-⌬⌬/TER1 reconstituted strain over 20 streaks, confirming that telomere attrition in the deletion strains was due to loss of the TER1 gene (Fig.…”

Study of Telomere Length Reveals Rapid Aging of Human Marrow Stromal Cells following In Vitro Expansion

“…This correlated with their ability to undergo more divisions, the preservation of a higher number of type I cells in culture, and the retention of in vitro efficient bone formation. The presence of a normal karyotype excludes mechanisms such as alternative lengthening of telomere as being responsible for the absence of telomere erosion [33]. No difference has been found in the bone marrow cellularity, number of progenitor cells, or age of the donor that could explain the extended proliferative capacity.…”

Telomerase Is Required to Protect Chromosomes with Vertebrate-type T2AG3 3′ Ends in Saccharomyces cerevisiae

“…Nevertheless, cellular backup mechanisms can maintain telomeres in the absence of telomerase and ultimately preserve genome integrity. In this mode of telomere maintenance, which is known as alternative lengthening of telomeres in human cells, and survivor mode in Saccharomyces cerevisiae, telomeric DNA is maintained via homologous recombination-based mechanisms (11,12).By differentiating chromosomal ends from internal ds breaks, telomeres also prevent chromosomal ends from eliciting DNA damage checkpoint activation and protect telomeres from inappropriate DNA repair activity. Binding of the multiprotein complex shelterin is essential for both protecting and maintaining the length of mammalian telomeres (13,14).…”

“…Nevertheless, cellular backup mechanisms can maintain telomeres in the absence of telomerase and ultimately preserve genome integrity. In this mode of telomere maintenance, which is known as alternative lengthening of telomeres in human cells, and survivor mode in Saccharomyces cerevisiae, telomeric DNA is maintained via homologous recombination-based mechanisms (11,12).…”