Regulation of telomere length and function by a Myb-domain protein in fission yeast

Abstract

Telomeres, the specialized nucleoprotein structures that comprise the ends of eukaryotic chromosomes^1,2, are essential for complete replication^3–5, and regulation of their length has been a focus of research on tumorigenesis^6–8. In the budding yeast Saccharomyces cerevisiae, the protein Raplp binds to telomeric DNA and functions in the regulation of telomere length^9–12. A human telomere protein, hTRF (human TTAGGG repeat factor) binds the telomere sequence in vitro¹³ and localizes to telomeres cytologically¹⁴, but its functions are not yet known. Here we use a genetic screen to identify a telomere protein in fission yeast, Tazlp (telomere-associated in Schizosaccharomyces pombe), that shares homology to the Myb proto-oncogene DNA-binding domain with hTRF. Disruption or deletion of the taz1⁺ gene causes a massive increase in telomere length. Tazlp is required for the repression of telomere-adjacent gene expression and for normal meiosis or sporulation. It may be a negative regulator of the telomere-replicating enzyme, telomerase^1,3, or may protect against activation of telomerase-independent pathways of telomere elongation⁸.