Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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]

PMID: 18828915

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Project description:Genomic instability associated with DNA replication stress is linked to cancer and genetic pathologies in humans. If not properly regulated, replication stress, such as fork stalling and collapse, can be induced at natural replication impediments present throughout the genome. The fork protection complex (FPC) is thought to play a critical role in stabilizing stalled replication forks at several known replication barriers including eukaryotic rDNA genes and the fission yeast mating-type locus. However, little is known about the role of the FPC at other natural impediments including telomeres. Telomeres are considered to be difficult to replicate due to the presence of repetitive GT-rich sequences and telomere-binding proteins. However, the regulatory mechanism that ensures telomere replication is not fully understood. Here, we report the role of the fission yeast Swi1/Timeless, a subunit of the FPC, in telomere replication. Loss of Swi1 causes telomere shortening in a telomerase-independent manner. Our epistasis analyses suggest that heterochromatin and telomere-binding proteins are not major impediments for telomere replication in the absence of Swi1. Instead, repetitive DNA sequences impair telomere integrity in swi1Î mutant cells, leading to the loss of repeat DNA. In the absence of Swi1, telomere shortening is accompanied with an increased recruitment of Rad52 recombinase and more frequent amplification of telomere/subtelomeres, reminiscent of tumor cells that utilize the alternative lengthening of telomeres pathway (ALT) to maintain telomeres. These results suggest that Swi1 ensures telomere replication by suppressing recombination and repeat instability at telomeres. Our studies may also be relevant in understanding the potential role of the FPC in regulation of telomere stability in cancer cells. Genome-wide distributions of Rad52 in wild type and in swi1 deletion in fission yeast The'SP1173_WT ChIP-seq' is an input sample (non-tagged data).

Dataset Information

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

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.

Similar Datasets

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