The Xpc gene markedly affects cell survival in mouse bone marrow
| Autor: | M.A. Suresh Kumar, Shari R. Hamilton, Cynthia Besch-Williford, Ahmad R. Safa, Martin L. Smith, Tabitha M. Hardy, Joshua L. Fischer, Karen E. Pollok, Travis W. Day |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Genetic Markers
Xeroderma pigmentosum Cell Survival DNA damage Health Toxicology and Mutagenesis Antineoplastic Agents Bone Marrow Cells Mice Transgenic Biology Toxicology Carboplatin Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Genetics medicine Animals Humans Cell Lineage Gene Genetics (clinical) 030304 developmental biology 0303 health sciences Models Genetic Cell Cycle Mutagenesis Cell cycle medicine.disease Original Papers DNA-Binding Proteins medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Immunology Cancer research Bone marrow DNA Damage Nucleotide excision repair |
| Zdroj: | Mutagenesis |
| ISSN: | 1464-3804 0267-8357 |
| DOI: | 10.1093/mutage/gep011 |
| Popis: | 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 approximately 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|