Telomere-related functions of yeast KU in the repair of bleomycin-induced DNA damage.

Bleomycins are small glycopeptide cancer chemotherapeutics that give rise to 3'-modified DNA double-strand breaks (DSBs). In Saccharomyces cerevisiae, DSBs are predominantly repaired by RAD52-dependent homologous recombination (HR) with some support by Yku70/Yku80 (KU)-dependent pathways. The main DSB repair function of KU is believed to be as part of the non-homologous ...
end-joining (NHEJ) pathway, but KU also functions in a "chromosome healing" pathway that seals DSBs by de novo telomere addition. We report here that rad52Deltayku70Delta double mutants are considerably more bleomycin hypersensitive than rad52Deltalig4Delta cells that lack the NHEJ-specific DNA ligase 4. Moreover, the telomere-specific KU mutation yku80-135i also dramatically increases rad52Delta bleomycin hypersensitivity, almost to the level of rad52Deltayku80Delta. The results indicate that telomere-specific functions of KU play a more prominent role in the repair of bleomycin-induced damage than its NHEJ functions, which could have important clinical implications for bleomycin-based combination chemotherapies.
Mesh Terms:
Antibiotics, Antineoplastic, Antigens, Nuclear, Bleomycin, DNA Damage, DNA Ligases, DNA Repair, DNA, Fungal, DNA-Binding Proteins, Microbial Viability, Mutation, Rad52 DNA Repair and Recombination Protein, Recombination, Genetic, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Telomere
Biochem. Biophys. Res. Commun.
Date: Jun. 08, 2007
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