Cancer progression is often associated with the accumulation of gross chromosomal rearrangements (GCRs), such as translocations, deletion of a chromosome arm, internal deletions or inversions. These malignancies are generally unresponsive to treatment and carry dismal prognoses. Not much is known about the processes that lead to genome rearrangements, what pathways might suppress rearrangements, and whether defects in these pathways underlie the ongoing genome instability seen in many cancers. This highlights a need for better understanding of the underlying biology, which hopefully will lead to better management of these malignancies.
Recent studies in yeast Saccharomyces cerevisiae have begun to uncover extensive and redundant pathways and genes that keep the rate of chromosomal rearrangements at very low levels. Human homologues of several of these genes have well-established roles as tumor suppressors, consistent with the hypothesis that the mechanisms preserving genomic stability in yeast are the same ones that go awry in cancer.
To look for the factors that prevent a loss of a chromosome arm (q- phenotype), Dr. Vuica-Ross has developed a genome-wide screen for terminal deletions in a yeast artificial chromosome (YAC) carrying human chromosome VII sequence flanked by several selectable markers. The YAC has been transferred into an isogenic set of yeast deletion mutants from the recently completed Yeast Genome Deletion Project. Dr. Vuica-Ross also has identified potentially novel chromosome integrity determinants and is currently characterizing them.
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