title: Non-homologous end joining is important for repair of Cr(VI)-induced DNA damage in Saccharomyces cerevisiae.
abstract: Hexavalent chromium is known to be a potent carcinogen that leads to many different DNA lesions, including DNA-protein crosslinks, and single- and double-strand breaks. In Saccharomyces cerevisiae, DNA double-strand breaks are mainly repaired by either homologous recombination (HR) or non-homologous end-joining (NHEJ) repair pathways. Here, we show that mutants deficient in NHEJ (yku70Delta, rad50Delta, dnl4Delta, mre11Delta, xrs2Delta) of S. cerevisiae are more sensitive to Cr(VI) toxic effects than wild-type cells. Also, a deletion mutant of SAE2 showed a similar sensitivity to Cr(VI), even though it has no apparent direct role in NHEJ. We also found that double mutants in HR and NHEJ (yku70Delta/rad52Delta, rad50Delta/rad52Delta, dnl4Delta/rad52Delta, mre11Delta/rad52Delta, xrs2Delta/rad52Delta) are synergistically more sensitive to Cr(VI) exposure than any of the single mutants, indicating that both repair pathways are involved in the repair of Cr(VI)-induced lesions. Finally, when the NHEJ mutants were exposed to Cr(VI) under anaerobic growth conditions, Cr(VI) toxicity was suppressed.
authors.affiliation: Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD 21702, USA. gustavo_santoyo@yahoo.com
authors.forename: Gustavo
authors.initials: G
authors.lastname: Santoyo
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Strathern
mesh_terms: D000693:Anaerobiosis; D002857:Chromium / Q000009:adverse effects*; D019457:Chromosome Breakage; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D004271:DNA, Fungal / Q000235:genetics*; D004720:Endonucleases; D009154:Mutation; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
chemical_list: D004271:DNA, Fungal; C107849:SAE2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D002857:Chromium; D004720:Endonucleases