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Analysis of the Mechanism by which Telomerase Impacts Chromosomal Stability and Cell Viability in Ku Mutants
Author(s) -
Holland Cory,
Lewis L Kevin
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1037-c
Subject(s) - telomerase , telomere , ku80 , ku70 , genome instability , homologous recombination , protein subunit , biology , microbiology and biotechnology , dna repair , saccharomyces cerevisiae , telomerase reverse transcriptase , dna , chromosome instability , non homologous end joining , dna damage , gene , genetics , dna binding protein , chromosome , transcription factor
The Ku complex is a heterodimer comprised of two subunits, Ku70 and Ku80, that binds double‐stranded DNA (dsDNA) ends. The Ku protein complex has multiple roles in DNA metabolism. The presence of Ku at the ends of the chromosomes protects the telomeres from degradation by nucleases and chromosomal recombination. Interestingly, Ku has also been shown to play a critical role in the non‐homologous end‐joining (NHEJ) pathway of repair of induced dsDNA strand breaks. In budding yeast ( Saccharomyces cerevisiae) , inactivation of either of the Ku subunit genes, YKU70 or YKU80 , abolishes NHEJ DNA repair and makes cells incapable of growing at elevated temperatures (37°C) due to telomere instability. The precise cause of telomere instability observed in yku70 ‐ mutants at high temperatures is unknown, but cell death can be alleviated by increasing levels of TLC1 , the RNA subunit of telomerase. Since the mechanism by which telomerase acts to rescue yku70 ‐ cells is still unknown, we are investigating the roles of TLC1 and other telomerase subunits in the rescue of Ku mutants. Work in our lab has shown that stabilization of telomeres in Ku ‐ cells is not dependent on the NHEJ or recombination DNA repair pathways. We are currently investigating regions of telomerase RNA required for telomere stabilization and how it serves as a scaffold for binding of both telomerase subunits as well as Ku.