Homologous Recombination and Translesion DNA Synthesis Play Critical Roles on Tolerating DNA Damage Caused by Trace Levels of Hexavalent Chromium

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  • Tian, Xu
    • Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
  • Patel, Keyur
    • Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
  • Ridpath, John R.
    • Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
  • Chen, Youjun
    • Affiliation: School of Medicine, Department of Neurology
  • Zhou, Yi-Hui
    • Other Affiliation: Department of Biological Sciences; North Carolina State University
  • Neo, Dayna
    • Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
  • Clement, Jean
    • Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
  • Takata, Minoru
    • Other Affiliation: Laboratory of DNA Damage Signaling; Department of Late Effects Studies; Radiation Biology Center; Kyoto University
  • Takeda, Shunichi
    • Other Affiliation: Department of Radiation Genetics; Graduate School of Medicine; Kyoto University
  • Sale, Julian
    • Other Affiliation: Medical Research Council Laboratory of Molecular Biology
  • Wright, Fred A.
    • Other Affiliation: Department of Biological Sciences; North Carolina State University
  • Swenberg, James A.
    • Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
    • Other Affiliation: University of North Carolina at Chapel Hill
  • Nakamura, Jun
    • Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
Abstract
  • Contamination of potentially carcinogenic hexavalent chromium (Cr(VI)) in the drinking water is a major public health concern worldwide. However, little information is available regarding the biological effects of a nanomoler amount of Cr(VI). Here, we investigated the genotoxic effects of Cr(VI) at nanomoler levels and their repair pathways. We found that DNA damage response analyzed based on differential toxicity of isogenic cells deficient in various DNA repair proteins is observed after a three-day incubation with K2CrO4 in REV1-deficient DT40 cells at 19.2 μg/L or higher as well as in TK6 cells deficient in polymerase delta subunit 3 (POLD3) at 9.8 μg/L or higher. The genotoxicity of Cr(VI) decreased ~3000 times when the incubation time was reduced from three days to ten minutes. TK mutation rate also significantly decreased from 6 day to 1 day exposure to Cr(VI). The DNA damage response analysis suggest that DNA repair pathways, including the homologous recombination and REV1- and POLD3-mediated error-prone translesion synthesis pathways, are critical for the cells to tolerate to DNA damage caused by trace amount of Cr(VI).
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  • Article
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  • In Copyright
Journal title
  • PloS One
Journal volume
  • 11
Journal issue
  • 12
Page start
  • e0167503
Language
  • English
ISSN
  • 1932-6203

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