The Saccharomyces cerevisiae telomeric Cdc13-Stn1-Ten1 complex regulates RNA pol II transcription

Abstract

In eukaryotes, specialized telomere protein complexes have an essential function in chromosome end protection and recruitment of telomerase to maintain telomere length constant. In the yeast Saccharomyces cerevisiae, these functions are taken in charge by the evolutionary conserved CST complex, composed of the Cdc13, Stn1 and Ten1 proteins. Here, we report the identification of genetic interactions between ten1 mutations and mutations in several genes coding for transcription regulators. Molecular assays confirmed that Ten1 is functionally linked to RNA pol II transcription. More precisely, the ten1-31 mutation caused a reduction in the occupancy of RNA pol II and the Spt5 elongation factor within transcribed genes. Moreover, CST physically associated with both Spt5 and the HMGB protein Hmo1. Very interestingly, we observed genome-wide that the promoters of genes down-regulated in the ten1-31 mutant are prefentially bound by Hmo1, which is known to mediate the architecture of RNA pol II S phase-transcribed genes. This, together with our finding that CST mutants need the Ctf18 and Mrc1 DNA replication checkpoints for survival, leads us to propose a working model in which CST, traveling with the replication fork, synchronizes transcription with replication fork progression following head-on collisions.