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PMID: 10454554 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Interactions of TLC1 (which encodes the RNA subunit of telomerase), TEL1, and MEC1 in regulating telomere length in the yeast Saccharomyces cerevisiae.

Molecular and cellular biology ·Vol. 19 ·No. 9 ·1999-09-00 ·Pages 6065-75

Ritchie KB, Mallory JC, Petes TD

Abstract

In the yeast Saccharomyces cerevisiae, chromosomes terminate with a repetitive sequence [poly(TG(1-3))] 350 to 500 bp in length. Strains with a mutation of TEL1, a homolog of the human gene (ATM) mutated in patients with ataxia telangiectasia, have short but stable telomeric repeats. Mutations of TLC1 (encoding the RNA subunit of telomerase) result in strains that have continually shortening telomeres and a gradual loss of cell viability; survivors of senescence arise as a consequence of a Rad52p-dependent recombination events that amplify telomeric and subtelomeric repeats. We show that a mutation in MEC1 (a gene related in sequence to TEL1 and ATM) reduces telomere length and that tel1 mec1 double mutant strains have a senescent phenotype similar to that found in tlc1 strains. As observed in tlc1 strains, survivors of senescence in the tel1 mec1 strains occur by a Rad52p-dependent amplification of telomeric and subtelomeric repeats. In addition, we find that strains with both tel1 and tlc1 mutations have a delayed loss of cell viability compared to strains with the single tlc1 mutation. This result argues that the role of Tel1p in telomere maintenance is not solely a direct activation of telomerase.

MeSH Terms
Ataxia Telangiectasia Mutated Proteins Base Sequence Cell Cycle Proteins DNA Primers/genetics DNA-Binding Proteins Fungal Proteins/genetics Genes, Fungal Humans Intracellular Signaling Peptides and Proteins Models, Genetic Molecular Sequence Data Mutation/genetics Nucleic Acid Conformation Phenotype Protein Conformation Protein Serine-Threonine Kinases Proteins/genetics RNA/chemistry,genetics,metabolism RNA, Fungal/chemistry,genetics,metabolism RNA, Long Noncoding RNA, Untranslated Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins Telomerase/chemistry,genetics,metabolism Telomere/metabolism Tumor Suppressor Proteins
Chemicals
Cell Cycle Proteins DNA Primers DNA-Binding Proteins Fungal Proteins Intracellular Signaling Peptides and Proteins Proteins RNA, Fungal RNA, Long Noncoding RNA, Untranslated Saccharomyces cerevisiae Proteins Tumor Suppressor Proteins telomerase RNA RNA ATM protein, human Ataxia Telangiectasia Mutated Proteins MEC1 protein, S cerevisiae Protein Serine-Threonine Kinases Telomerase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ritchie K B
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3280, USA.
Mallory J C
Petes T D
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.9.6065
Published
1999-09-00
Pages
6065-75
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC84515
Subset
IM
Grants
NIGMS NIH HHS · R01 GM024110 · United States
NIGMS NIH HHS · GM24110 · United States
External Links
PubMed source DOI: 10.1128/MCB.19.9.6065 PMC Full Text View journal details
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