Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of yeast strains harbouring a temperature sensitive allele of the essential telomere capping gene cdc13-1 to investigate the genome-wide response to uncapped telomeres


ABSTRACT: Telomeres are nucleoprotein complexes that protect the ends of eukaryotic chromosomes from being recognised as double strand breaks. When telomere structure is perturbed, a co-ordinated series of events to promote arrest of the cell cycle is rapidly initiated so that cells carrying damaged telomeres do not continue to divide. In order to better understand the eukaryotic response to telomere damage, we employed budding yeast strains harbouring a temperature sensitive allele of an essential telomere capping gene (cdc13-1) and conducted a transcriptomic study of the genome-wide response to uncapped telomeres. We show that telomere uncapping in cdc13-1 strains is associated with the differential expression of over 1100 genes and has features in common with the responses to DNA damage, diverse environmental stresses and, as expected, the absence of telomerase. The transcriptomic response to telomere uncapping includes many genes with known roles in telomere function and some features that appear to be unique. BNA2 is the second most highly up-regulated gene upon telomere uncapping in cdc13-1 strains and is required for the biosynthesis of NAD+. We have shown that deletion of BNA2 and other genes involved in NAD+ synthesis, suppresses the temperature sensitivity of cdc13-1 strains. NAD+ synthetic genes may therefore play previously unknown roles in the cellular response to telomere uncapping.

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Dan Swan 

PROVIDER: E-MEXP-1551 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A genome wide analysis of the response to uncapped telomeres in budding yeast reveals a novel role for the NAD+ biosynthetic gene BNA2 in chromosome end protection.

Greenall Amanda A   Lei Guiyuan G   Swan Daniel C DC   James Katherine K   Wang Liming L   Peters Heiko H   Wipat Anil A   Wilkinson Darren J DJ   Lydall David D  

Genome biology 20081001 10


<h4>Background</h4>Telomeres prevent the ends of eukaryotic chromosomes from being recognized as damaged DNA and protect against cancer and ageing. When telomere structure is perturbed, a co-ordinated series of events promote arrest of the cell cycle so that cells carrying damaged telomeres do not divide. In order to better understand the eukaryotic response to telomere damage, budding yeast strains harboring a temperature sensitive allele of an essential telomere capping gene (cdc13-1) were sub  ...[more]

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