Telomere Maintenance and Survival in Saccharomyces cerevisiae in the Absence of Telomerase and RAD52

Abstract

Telomeres are essential features of linear genomes that are crucial for chromosome stability. Telomeric DNA is usually replenished by telomerase. Deletion of genes encoding telomerase components leads to telomere attrition with each cycle of DNA replication, eventually causing cell senescence or death. In the Saccharomyces cerevisiae strain W303, telomerase-null populations bypass senescence and, unless EXO1 is also deleted, this survival is RAD52 dependent. Unexpectedly, we found that the S. cerevisiae strain S288C could survive the removal of RAD52 and telomerase at a low frequency without additional gene deletions. These RAD52-independent survivors were propagated stably and exhibited a telomere organization typical of recombination between telomeric DNA tracts, and in diploids behaved as a multigenic trait. The polymerase-d subunit Pol32 was dispensable for the maintenance of RAD52-independent survivors. The incidence of this rare escape was not affected by deletion of other genes necessary for RAD52-dependent survival, but correlated with initial telomere length. If W303 strains lacking telomerase and RAD52 first underwent telomere elongation, rare colonies could then bypass senescence. We suggest that longer telomeres provide a more proficient substrate for a novel telomere maintenance mechanism that does not rely on telomerase, RAD52, or POL32.

Mgm101: A double-duty Rad52-like protein

“…The possibility of genetic interaction between ICL repair factors and Rad52-dependent recombination event(s) in the process of telomere elongation was also examined. In agreement with previous observations, extensive telomere elongation is observed in rad52 cells 65 . Importantly, deletion of either Pso2-dependent or FA-like pathway in rad52 cells resulted in the recovery of the wild-type telomere length.…”

Telomerase reverse transcriptase-dependent telomere equilibration mitigates tissue dysfunction in mTert heterozygotes

“…The impact of the initial telomere length on subsequent telomere dynamics is not without precedent. In S. cerevisiae strains that possess longer telomeres, rare cells can survive the loss of telomerase and RAD52, this survival does not occur in populations with shorter telomeres (Grandin and Charbonneau, 2009;LeBel et al, 2009). Our data suggest that the response to prolonged telomerase heterozygosity could similarly be influenced by the initial telomere length.…”

Polymerase Epsilon Is Required To Maintain Replicative Senescence

“…Replicative senescence in this model system is similar to human replicative senescence, because most human somatic cells do not express telomerase and do not undergo alternative lengthening of telomeres (ALT). Cells in the tlc1⌬ rad52⌬ background arrest the cell cycle within a few days and remain arrested until death (17). Therefore, the signal(s) for cell cycle arrest in response to telomere attrition would also be expected to last until cellular death.…”

“…We introduce the term "ALTOS" to describe the outcome of any pathway able to maintain/elongate (sub) telomeres in the absence of telomerase. ALTOS survivors could be either Rad52 dependent or Rad52 independent (13,17). Budding yeast cells from most-genetic backgrounds do not form ALTOS survivors in the absence of Rad52.…”