title: NET1 and HFI1 genes of yeast mediate both chromosome maintenance and mitochondrial rho(-) mutagenesis.
abstract: An increase in the mitochondrial rho(-) mutagenesis is a well-known response of yeast cells to mutations in numerous nuclear genes as well as to various kinds of stress. Despite extensive studies for several decades, the biological significance of this response is still not fully understood. The genetic approach to solving this enigma includes a study of genes that are required for the high incidence of spontaneous rho(-) mutants. We have obtained mutations of a few nuclear genes of that sort and found that mutations in certain genes, including CDC28, the central cell-cycle regulation gene, result in a decrease in spontaneous rho(-) mutability and simultaneously affect the maintenance of the yeast chromosomes and plasmids. Two more genes resembling CDC28 in this respect are identified in the present work as a result of the characterization of four new mutants. These two genes are NET1 and HFI1 which mediate important regulatory protein-protein interactions in the yeast cell. The effects of four mutations, including net1-srm and hfi1-srm, on the maintenance of the yeast mitochondrial genome, chromosomes and plasmids, as well as on the cell's sensitivity to ionizing radiation, are also described. The data presented suggest that the pleiotropic srm mutations determining coordinate changes in the fidelity of mitotic transmission of chromosomes, plasmids and mtDNA molecules identify genes that most probably operate high up in the hierarchy of the general genetic regulation of yeast.
authors.affiliation: Joint Institute for Nuclear Research, Moscow Region, 141980 Dubna, Russia. koltovaya@jinr.ru
authors.forename: N A
authors.initials: NA
authors.lastname: Koltovaya
authors.forename: A S
authors.initials: AS
authors.lastname: Guerasimova
authors.forename: I A
authors.initials: IA
authors.lastname: Tchekhouta
authors.forename: A B
authors.initials: AB
authors.lastname: Devin
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins / Q000235:genetics*; D015825:Chromosomes, Fungal / Q000235:genetics*; D003001:Cloning, Molecular; D005720:Gamma Rays; D005800:Genes, Fungal / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics*; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics; D011839:Radiation, Ionizing; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics*; D014170:Transformation, Genetic / Q000502:physiology; D019061:src-Family Kinases / Q000235:genetics
chemical_list: D000209:Acute-Phase Proteins; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C106162:HFI1 protein, S cerevisiae; C119300:Net1 protein, S cerevisiae; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; C010781:acute-phase protein rho; C089510:SRMS protein, human; D019061:src-Family Kinases