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

Lookup NU author(s): Professor David Lydall, Dr Laura Maringele

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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 RAL52 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 its a multigenic trait. The polymerase-8 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.


Publication metadata

Author(s): LeBel C, Rosonina E, Sealey DCF, Pryde F, Lydall D, Maringele L, Harrington LA

Publication type: Article

Publication status: Published

Journal: Genetics

Year: 2009

Volume: 182

Issue: 3

Pages: 671-684

ISSN (print): 0016-6731

ISSN (electronic): 1943-2631

Publisher: Genetics Society of America

URL: http://dx.doi.org/10.1534/genetics.109.102939

DOI: 10.1534/genetics.109.102939


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Funding

Funder referenceFunder name
G0800081-85694Medical Research Council United Kingdom
HHMI 55005945Howard Hughes Medical Institute international Scholar Award Program
R01 AG02198)National Institute on Aging (National Institutes of Health)
WT 075294Wellcome Trust
WT 081164Wellcome Trust
WT 084637Wellcome Trust

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