title: Oxygen metabolism and reactive oxygen species cause chromosomal rearrangements and cell death.
abstract: The absence of Tsa1, a key peroxiredoxin that functions to scavenge H(2)O(2) in Saccharomyces cerevisiae, causes the accumulation of a broad spectrum of mutations including gross chromosomal rearrangements (GCRs). Deletion of TSA1 also causes synthetic lethality in combination with mutations in RAD6 and several key genes involved in DNA double-strand break repair. In the present study we investigated the causes of GCRs and cell death in these mutants. tsa1-associated GCRs were independent of the activity of the translesion DNA polymerases zeta, eta, and Rev1. Anaerobic growth reduced substantially GCR rates of WT and tsa1 mutants and restored the viability of tsa1 rad6, tsa1 rad51, and tsa1 mre11 double mutants. Anaerobic growth also reduced the GCR rate of rad27, pif1, and rad52 mutants, indicating a role of reactive oxygen species in GCR formation in these mutants. In addition, deletion of TSA1 or H(2)O(2) treatment of WT cells resulted in increased formation of Rad52 foci, sites of repair of multiple DNA lesions. H(2)O(2) treatment also induced the GCRs. Our results provide in vivo evidence that oxygen metabolism and reactive oxygen species are important sources of DNA damages that can lead to GCRs and lethal effects in S. cerevisiae.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 2027, Institut Curie, Bâtiment 110, Centre Universitaire, 91405 Orsay, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ragu
authors.forename: Gérard
authors.initials: G
authors.lastname: Faye
authors.forename: Ismail
authors.initials: I
authors.lastname: Iraqui
authors.forename: Amélie
authors.initials: A
authors.lastname: Masurel-Heneman
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kolodner
authors.forename: Meng-Er
authors.initials: ME
authors.lastname: Huang
mesh_terms: D000693:Anaerobiosis; D043171:Chromosomal Instability / Q000187:drug effects / Q000502:physiology*; D004249:DNA Damage; D017353:Gene Deletion; D005800:Genes, Fungal / Q000235:genetics; D006861:Hydrogen Peroxide / Q000633:toxicity; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000235:genetics; D010100:Oxygen / Q000378:metabolism*; D010544:Peroxidases / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
chemical_list: D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; D010544:Peroxidases; C496253:Tsa1 protein, S cerevisiae; D010100:Oxygen