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

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.

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Greenall A, Lei G, Swan DC, James K, Wang L, Peters H, Wipat A, Wilkinson DJ, Lydall D