Book of Abstracts: Albany 2005
Recruiting Telomerase to Different Kinds of DNA Ends: A Role for Ku
Ku is a conserved DNA end-binding protein that plays different roles at different kinds of DNA ends. At telomeres, Ku is part of the protective structure that prevents the chromosome end from undergoing degradation or end-to-end fusion. By contrast, at broken DNA ends that arise from DNA damage, Ku actively promotes end-to-end fusion as part of the nonhomologous end-joining pathway of DNA repair. Recently, we have identified a new role for Ku -- in recruiting telomerase to DNA ends -- that impacts both telomere length maintenance and DNA repair in Saccharomyces cerevisiae. We show that Ku physically binds the RNA component of telomerase, TLC1, via a 48 nt stem-loop motif. We have also isolated a novel allele of Ku that is specifically defective in TLC1 RNA binding. Telomeres are short and the kinetics of new telomere addition are slow in strains harboring this Ku allele, whereas other Ku-dependent activities are unaffected. These results suggest that the Ku-TLC1 RNA interaction is important for efficient telomerase activity at telomeres. We also find that the interaction between Ku and telomerase provides the cell with an alternative means of DNA repair, namely healing a broken chromosome by de novo telomere addition. Work is underway to determine when and how Ku recruits telomerase to broken DNA ends, and to investigate whether certain types of DNA damage rely on this mechanism for DNA repair.
Department of Biology