Telomere-related functions of yeast KU in the repair of bleomycin-induced DNA damage |
| |
Authors: | Tam Angela T Y Pike Brietta L Hammet Andrew Heierhorst Jörg |
| |
Institution: | St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Vic. 3065, Australia. |
| |
Abstract: | 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. |
| |
Keywords: | DNA repair Double-strand break Bleomycin Telomere Homologous recombination Non-homologous end-joining Yeast |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|