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 cellula r 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. R. Hartwell, Genes Dev. 8:652-665, 1994), In wild-type yeast cells, genes inserted near the telomeres are tra nscriptionally silenced (D. E. Gottschling, O. M. Aparichio, B. L. Billingt on, and V. A. Zakian, Cell 63:751-762, 1990), We show that mec1 strains hav e reduced ability to silence gene expression near the telomere, This defici ency was alleviated by the sml1 mutation. Overexpression of Mec1p also resu lted in a silencing defect, although this overexpression did not affect the checkpoint function of Mec1p. Telomeric silencing was not affected by muta tions in several other genes in the Mec1p checkpoint pathway (null mutation s 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 i n mec1 strains was not a consequence of the slightly shortened telomeres ob served in these strains.