The Xpc gene markedly affects cell survival in mouse bone marrow

Joshua L. Fischer, M. A.Suresh Kumar, Travis W. Day, Tabitha M. Hardy, Shari Hamilton, Cynthia Besch-Williford, Ahmad R. Safa, Karen E. Pollok, Martin L. Smith

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The XPC protein (encoded by the xeroderma pigmentosum Xpc gene) is a key DNA damage recognition factor that is required for global genomic nucleotide excision repair (G-NER). In contrast to transcription-coupled nucleotide excision repair (TC-NER), XPC and G-NER have been reported to contribute only modestly to cell survival after DNA damage. Previous studies were conducted using fibroblasts of human or mouse origin. Since the advent of Xpc-/- mice, no study has focused on the bone marrow of these mice. We used carboplatin to induce DNA damage in Xpc-/- and strain-matched wild-type mice. Using several independent methods, Xpc-/- bone marrow was ∼10-fold more sensitive to carboplatin than the wild type. Importantly, 12/20 Xpc-/- mice died while 0/20 wild-type mice died. We conclude that G-NER, and XPC specifically, can contribute substantially to cell survival. The data are important in the context of cancer chemotherapy, where Xpc gene status and G-NER may be determinants of response to DNA-damaging agents including carboplatin. Additionally, altered cell cycles and altered DNA damage signalling may contribute to the cell survival end point.

Original languageEnglish (US)
Pages (from-to)309-316
Number of pages8
JournalMutagenesis
Volume24
Issue number4
DOIs
StatePublished - Jul 2009

ASJC Scopus subject areas

  • Genetics
  • Toxicology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

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  • Cite this

    Fischer, J. L., Kumar, M. A. S., Day, T. W., Hardy, T. M., Hamilton, S., Besch-Williford, C., Safa, A. R., Pollok, K. E., & Smith, M. L. (2009). The Xpc gene markedly affects cell survival in mouse bone marrow. Mutagenesis, 24(4), 309-316. https://doi.org/10.1093/mutage/gep011