Skip to main content
Open Access Publications from the University of California

UC San Diego

UC San Diego Electronic Theses and Dissertations bannerUC San Diego

Checkpoint gene interactions that suppress genome instability in Saccharomyces cerevisiae /


Genome instability, which includes mutations in gene sequences, aneuploidy, and gross chromosomal rearrangements (GCRs), is a common characteristic of cancer. Genome instability can be caused by several genetic defects including defects in DNA damage and replication checkpoint pathways; such defects are also known to play a role in the formation and progression of cancer. However, the cellular pathways that interact with the checkpoint responses to maintain genome stability are not well understood. To identify such pathways in Saccharomyces cerevisiae, double mutant strains were generated by systematically crossing query strains containing a GCR assay (the duplication-mediated GCR assay) and mutations in individual checkpoint genes (rad17, mec1, rad9, mrc1, mrc1-aq, rad53, chk1, and dun1) with an array of 632 strains containing deletions of individual genes implicated in preventing GCRs. The double mutant strains were then analyzed for GCR formation using a semi- quantitative scoring system. A complex-by-complex approach was used to identify robust interactions. Using this analysis, 20 complexes were identified that interacted with the checkpoint pathways to suppress GCR formation. These 20 complexes included genes involved in DNA repair or the DNA damage response, histone modification and transcription, and other functions. Further mechanistic studies of these complexes can be used to elucidate pathways and interactions previously unknown to suppress cancer-related genome instability

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View