Regulation of Human HRAS1 Minisatellite Stability During Stationary Phase

Abstract

Minisatellites are repetitive tracts of DNA with repeat units ranging from 16-100 base pairs in length. They are stable during mitosis but display changes in repeat number and order after meiosis. Rare alleles of minisatellite tracts thought to arise from repeat instability are associated with human diseases, including cancer, diabetes, and epilepsy. The stability of minisatellites in non-proliferating stationary phase cells is not well understood. Previous work has shown that the zinc transporter ZRT1, the checkpoint gene RAD53, the DNA repair gene RAD27, the endocytosis gene END3, and the protein kinase PKC1 regulate the stability of minisatellites in S. cerevisiae during stationary phase. We inserted the human minisatellite associated with HRAS1 into the ADE2 gene to determine how its stability is regulated during stationary phase. Loss of ZRT1, RAD27, or RAD53 destabilized the minisatellite; loss of PKC1 or END3 had no effect. This work contributes significantly to our understanding of repeat stability and genome stability during stationary phase; this has important implications for human genome stability, since most human somatic cells are non-proliferating.