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 Safa, Karen Pollok, Martin L. Smith

Research output: Contribution to journalArticle

6 Citations (Scopus)

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

Fingerprint

Cell Survival
Bone
Repair
DNA Repair
Nucleotides
Genes
Bone Marrow
Cells
Carboplatin
DNA Damage
DNA
Chemotherapy
Xeroderma Pigmentosum
Transcription
Fibroblasts
Cell Cycle
Drug Therapy
Proteins
Neoplasms

ASJC Scopus subject areas

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

Cite this

Fischer, J. L., Kumar, M. A. S., Day, T. W., Hardy, T. M., Hamilton, S., Besch-Williford, C., ... 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

The Xpc gene markedly affects cell survival in mouse bone marrow. / Fischer, Joshua L.; Kumar, M. A Suresh; Day, Travis W.; Hardy, Tabitha M.; Hamilton, Shari; Besch-Williford, Cynthia; Safa, Ahmad; Pollok, Karen; Smith, Martin L.

In: Mutagenesis, Vol. 24, No. 4, 07.2009, p. 309-316.

Research output: Contribution to journalArticle

Fischer, JL, Kumar, MAS, Day, TW, Hardy, TM, Hamilton, S, Besch-Williford, C, Safa, A, Pollok, K & Smith, ML 2009, 'The Xpc gene markedly affects cell survival in mouse bone marrow', Mutagenesis, vol. 24, no. 4, pp. 309-316. https://doi.org/10.1093/mutage/gep011
Fischer JL, Kumar MAS, Day TW, Hardy TM, Hamilton S, Besch-Williford C et al. The Xpc gene markedly affects cell survival in mouse bone marrow. Mutagenesis. 2009 Jul;24(4):309-316. https://doi.org/10.1093/mutage/gep011
Fischer, Joshua L. ; Kumar, M. A Suresh ; Day, Travis W. ; Hardy, Tabitha M. ; Hamilton, Shari ; Besch-Williford, Cynthia ; Safa, Ahmad ; Pollok, Karen ; Smith, Martin L. / The Xpc gene markedly affects cell survival in mouse bone marrow. In: Mutagenesis. 2009 ; Vol. 24, No. 4. pp. 309-316.
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