title: Comparative Effects of Mercury(II) and Cadmium on MutS Homolog 6(MSH6)-Mediated DNA Mismatch Binding Activities in Zebrafish (Danio rerio) Embryos.
abstract: MutS homolog 6 (MSH6) of the MSH2-MSH6 complex binds simple mispairs and small insertion-deletion loops (IDL) then initiates DNA mismatch repair in eukaryotes. We have shown the ability of Cd(2+) to downregulate msh2/msh6 expression in zebrafish embryos via oxidative stress. This study explored the effects of Cd(2+) and Hg(2+) on MSH6-mediated mismatch binding activities. MSH6-mediated G-T and IDL-specific binding activities were significantly inhibited at similar levels after exposing zebrafish embryos at 1 h postfertilization) to HgCl2 or CdCl2 at 1.0 to 2.5 μM for 9 h, but MSH6 synthesis was found to be less sensitive to Hg(2+) than to Cd(2+) . Real-time RT-PCR and in situ hybridization also detected a weaker susceptibility of MSH gene transcription to Hg(2+) . The weaker response of MSH gene activities to Hg(2+) correlated with the lower oxidative stress-inducing potential of Hg(2+) . Hence, Hg(2+) targets mismatch sensing capacity at protein function rather than at transcription level.
authors.affiliation: Department of Bioscience and Biotechnology and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, 20224, Taiwan, Republic of China.
authors.forename: Tsung-Nan
authors.initials: TN
authors.lastname: Ho
authors.affiliation: Department of Bioscience and Biotechnology and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, 20224, Taiwan, Republic of China.
authors.forename: Shih-Tsung
authors.initials: ST
authors.lastname: Sung
authors.affiliation: Department of Bioscience and Biotechnology and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, 20224, Taiwan, Republic of China.
authors.forename: Kuan-Ming
authors.initials: KM
authors.lastname: Huang
authors.affiliation: Department of Bioscience and Biotechnology and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, 20224, Taiwan, Republic of China. toddhsu@mail.ntou.edu.tw.
authors.forename: Todd
authors.initials: T
authors.lastname: Hsu
mesh_terms: D000818:Animals; D020137:Base Pair Mismatch; D002104:Cadmium / Q000633:toxicity*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008628:Mercury / Q000633:toxicity*; D018384:Oxidative Stress; D011485:Protein Binding; D015027:Zebrafish / Q000196:embryology*
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D002104:Cadmium; D008628:Mercury
keywords: Cadmium; Mercury; Mismatch Repair; MutS homologs; Zebrafish