Multiple Pathways Regulate Minisatellite Stability During Stationary Phase in Yeast

G3: Genes, Genomes, Genetics

David T. Kirkpatrick²  Maire K. Kelly²  Peter A. Jauert²  Maitreya J. Dunham¹  Laura Brosnan² 

[1] Department of Genome Sciences, University of Washington, Seattle, Washington 98195Department of Genome Sciences, University of Washington, Seattle, Washington 98195Department of Genome Sciences, University of Washington, Seattle, Washington 98195;Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455

关键词: DNA stability;    stationary phase;    G0;    quiescence;   

DOI  :  10.1534/g3.112.003673

学科分类：生物科学（综合）

来源: Genetics Society of America

【 摘 要 】

Alterations in minisatellite DNA repeat tracts in humans have been correlated with a number of serious disorders, including cancer. Despite their importance for human health, the genetic factors that influence minisatellite stability are not well understood. Previously, we identified mutations in the Saccharomyces cerevisiae zinc homeostasis genes ZRT1 and ZAP1 that significantly increase the frequency of minisatellite alteration specifically during stationary phase. In this work, we identified mutants of END3, PKC1, and RAD27 that increase minisatellite instability during stationary phase. Genetic analysis reveals that these genes, along with ZRT1 and ZAP1, comprise multiple pathways regulating minisatellite stability during stationary phase. Minisatellite alterations generated by perturbation of any of these pathways occur via homologous recombination. We present evidence that suggests formation of ssDNA or ssDNA breaks may play a primary role in stationary phase instability. Finally, we examined the roles of these pathways in the stability of a human minisatellite tract associated with the HRAS1 oncogene and found that loss of RAD27, but not END3 or PKC1, destabilizes the HRAS1 minisatellite in stationary phase yeast. This result indicates that the genetic control of stationary phase minisatellite stability is dependent on the sequence composition of the minisatellite itself.

【 授权许可】

Unknown