Telomere Maintenance in the Absence of Telomerase.
Abstract
Telomeres, ends of eukaryotic chromosomes, need to be maintained for long-term cellular proliferation. In most eukaryotes, the reverse transcriptase telomerase is responsible for replicating and maintaining the telomeres. Absence of telomerase activity results in progressive telomere shortening with continued cell division. When telomeres are too short to maintain function, most cells stop dividing. However, a subpopulation of cells can escape death via telomerase-independent pathway(s). Telomerase-independent survivors have been observed in budding yeasts, in fission yeast and in human cells. In S. cerevisiae survivors, two types of telomeric sequences are affected: the terminal G(1-3)T repeats and subtelomeric repeats called Y' elements; both sequences are substantially amplified by RAD52-dependent recombination. Since the terminal U-rich sequences are not perfectly homologous, this could provide a potential barrier to recombination. We have tested this, by demonstrating that mutations in genes in the mismatch repair pathway, previously shown to increase homeologous recombination frequencies, enhance telomerase-independent survival in a RAD52-dependent manner. Since little or no Y' amplification is observed in these survivors compared to just telomerase-minus survivors, this suggests that the absence of mismatch repair genes removes a block to G(1-3)T to G(1-3)T recombination.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 1999
- Accession Number
- ADA369622
Entities
People
- Aylin Rizki
Organizations
- Baylor College of Medicine