Genetic Instability and Checkpoint Genes: Insights from a Single Eucaryote (S.Cerevisiae) for Human Breast Cancer

摘要

Our goals in this proposal were as follows. First, we are analyzing therelationship between checkpoint gene functions and four types of genomic instability in Saccharomyces cerevisiae, a simple eucaryotic cell. We have now extended this study to analysis of an instance of genomic instability we call 'unstable 7', which has many features suggesting it may be useful in understanding genomic instability in checkpoint mutant cells. Second, we wanted to isolate human checkpoint genes by complementation. Our efforts have not been successful in this regard. To develop new strategies, we have turned to a detailed analysis of a MEC1-like gene, called TELl, that can partially suppress mec1 mutant defects. These studies will provide some information on order of gene function in checkpoint pathways. This studies of TELl may also identify experimental conditions to identify human checkpoint genes by complementation. We anticipate these studies will further our basic knowledge of checkpoint gene function and enhance our understanding of mechanisms of genomic instability in tumor cells.