Exploring the Role of Genetic Modifiers in DNA Repair and Breast Cancer
Annual summary 1 Sep 2009-31 Aug 2013
FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
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In this study, I have performed a genome-wide screen for gene-gene interactions which cause sensitivity to DNA damage in the yeast Saccharomyces cerevisiae in an attempt to identify genetic factors which cause predisposition to breast cancer. I have identified 13 TEL1 ATM ortholog interactions which cause enhanced sensitivity to the DNA damaging agent MMS. Surprisingly, many of these interactions confer a significant defect in telomere metabolism.Restoration of normal telomere lengths in the tel1 xxx double mutants results in only minor suppression of the DNA damage sensitivity, demonstrating that the sensitivity of these mutants must also involve mechanisms independent of telomere length. In support of a model for increased replication stress in the tel1 xxx double mutants, I show that depletion of dNTP pools through pre-treatment with hydroxyurea renders tel1 cells but not wild-type MMS-sensitive, demonstrating that under certain conditions, Tel1p does indeed play a critical role in the DDR.
- Anatomy and Physiology
- Medicine and Medical Research