Involvement of the checkpoint protein Mec1p in silencing of gene expression at telomeres in Saccharomyces cerevisiae

Yeast strains with a mutation in the MEC1 gene are deficient in the cellular checkpoint response to DNA-damaging agents and have short telomeres (K. B. Ritchie, J. C. Mallory, and T. D. Petes, Mol. Cell. Biol. 19: 6065- 6075, 1999; T. A. Weinert, G. L. Kiser, and L. H. Hartwell, Genes Dev. 8:652- 665, 1994). In wild-type yeast cells, genes inserted near the telomeres are transcriptionally silenced (D. E. Gottschling, O. M. Aparichio, B. L. Billington, and V. A. Zakian, Cell 63:751-762, 1990). We show that mec1 strains have reduced ability to silence gene expression near the telomere. This deficiency was alleviated by the sml1 mutation. Overexpression of Mec1p also resulted in a silencing defect, although this overexpression did not affect the checkpoint function of Mec1p. Telomeric silencing was not affected by mutations in several other genes in the Mec1p checkpoint pathway (null mutations in RAD9 and CHK1 or in several hypomorphic rad53 alleles) but was reduced by a null mutation of DUN1. In addition, the loss of telomeric silencing in mec1 strains was not a consequence of the slightly shortened telomeres observed in these strains.