Telomerase-independent proliferation is influenced by cell type in Saccharomyces cerevisiae.
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 MATalpha 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 MATalpha 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.
Lowell
Joanna E
JE
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, USA.
Roughton
Alexander I
AI
Lundblad
Victoria
V
Pillus
Lorraine
L
D000375:Aging / Q000235:genetics*; D015139:Blotting, Southern; D004268:DNA-Binding Proteins / Q000502:physiology*; D004587:Electrophoresis, Agar Gel; D020868:Gene Silencing; D005800:Genes, Fungal / Q000235:genetics; D049770:Genes, Mating Type, Fungal; D018398:Homeodomain Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010957:Plasmids; D051721:Rad52 DNA Repair and Recombination Protein; D011995:Recombination, Genetic / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C096063:MATA1 protein, S cerevisiae; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D019098:Telomerase