Genetics, Vol. 164, 909-921, July 2003, Copyright © 2003

Telomerase-Independent Proliferation Is Influenced by Cell Type in Saccharomyces cerevisiae

Joanna E. Lowella, Alexander I. Roughtonb, Victoria Lundbladc, and Lorraine Pillusb
a Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215,
b Division of Biological Sciences, Section of Molecular Biology and Center for Molecular Genetics and UCSD Cancer Center, University of California, San Diego, California 92093-0347
c Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030

Corresponding author: Lorraine Pillus, 9500 Gilman Dr., University of California, San Diego, CA 92093-0347., lpillus{at}biomail.ucsd.edu (E-mail)

Communicating editor: F. WINSTON

Yeast strains harboring mutations in genes required for telomerase function (TLC1 and the EST genes) exhibit progressive shortening of telomeric DNA and replicative senescence. A minority of cells withstands loss of telomerase through RAD52-dependent amplification of telomeric and subtelomeric sequences; such survivors are now capable of long-term propagation with telomeres maintained by recombination rather than by telomerase. Here we report that simultaneous expression in haploid cells of both MATa and MAT{alpha} information suppresses the senescence of telomerase-deficient mutants, with suppression occurring via the RAD52-dependent survivor pathway(s). Such suppression can be mimicked by deletion of SIR1–SIR4, genes that function in transcriptional silencing of several loci including the silent mating-type loci. Furthermore, telomerase-defective diploid strains that express only MATa or MAT{alpha} information senesce at a faster rate than telomerase-defective diploids that are heterozygous at the MAT locus. This suggests that the RAD52-dependent pathway(s) for telomere maintenance respond to changes in the levels of recombination, a process regulated in part by the hierarchy of gene control that includes MAT regulation. We propose that cell-type-specific regulation of recombination at human telomeres may similarly contribute to the tissue-specific patterns of disease found in telomerase-deficient tumors.




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