title: Boric acid-dependent decrease in regulatory histone H3 acetylation is not mutagenic in yeast.
abstract: Candida albicans is a dimorphic yeast commonly found on human mucosal membranes that switches from yeast to hyphal morphology in response to environmental factors. The change to hyphal growth requires histone H3 modifications by the yeast-specific histone acetyltransferase Rtt109. In addition to its role in morphogenesis, Rtt109-dependent acetylation of histone H3 lysine residues 9 and 56 has regulatory functions during DNA replication and repair. Boric acid (BA) is a broad-spectrum agent that specifically inhibits C. albicans hyphal growth, locking the fungus in its harmless commensal yeast state. The present study characterizes the effect of BA on C. albicans histone acetylation in respect to specificity, time-course and significance. We demonstrate that sublethal concentrations of BA reduce H3K9/H3K56 acetylation, both on a basal level and in response to genotoxic stress. Acetylation at other selected histone sites were not affected by BA. qRT-PCR expression analysis of the DNA repair gene Rad51 indicated no elevated level of genotoxic stress during BA exposure. A forward-mutation analysis demonstrated the BA does not increase spontaneous or induced mutations. The findings suggest that DNA repair remains effective even when histone H3 acetylation decreases and dispels the notion that BA treatment impairs genome integrity in yeast.
authors.affiliation: Department of Biochemistry and Nutrition, Des Moines University, 3200 Grand Avenue, Des Moines, IA 50312, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Pointer
authors.affiliation: Department of Biochemistry and Nutrition, Des Moines University, 3200 Grand Avenue, Des Moines, IA 50312, USA mschmidt@dmu.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D000107:Acetylation / Q000187:drug effects; D001888:Boric Acids / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D016681:Genome, Fungal / Q000187:drug effects; D051548:Histone Acetyltransferases; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D025301:Hyphae; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D016296:Mutagenesis; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001888:Boric Acids; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D008741:Methyl Methanesulfonate; D051548:Histone Acetyltransferases
keywords: Candida albicans; boric acid; histone acetylation; mutagenesis