Evidence that nucleotide excision repair is attenuated in bax-deficient mammalian cells following ultraviolet irradiation.
Nonmelanoma skin cancer (NMSC) is the most frequently diagnosed form of cancer in United States. We have previously described the tumor suppressor role of bax protein in skin carcinogenesis as well as the ability of bax to modulate the apoptotic response of keratinocytes following ultraviolet irradiation. Moreover, we have demonstrated an increase in tumor incidence in bax-null mice compared to control littermates in an in vivo chemical carcinogenesis experiment. In this study, we examined the contribution of bax protein in repair of UVR-mediated DNA lesions. The level of cyclobutane pyrimidine dimers remaining was twofold greater in UVR-treated primary keratinocytes from bax-deficient mice than that of control cells at 48 h (P < 0.03). Similar results were obtained using embryonic fibroblasts and also with a bax-deficient prostate cancer cell line. However, the repair rate of 6-4 pyrimidine pyrimidone photoproducts was unaffected by the absence of bax protein. These findings suggest that bax may have a dual function in its role as tumor suppressor in NMSC. Bax may directly or indirectly facilitate either DNA repair or cell death. Either function would be anticipated to enhance genomic integrity following a genotoxic event through repair or deletion of the damaged cell.
Cho
Song
S
Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
O'Connor
Sean L
SL
McDonnell
Timothy J
TJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004247:DNA / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects; D005347:Fibroblasts; D015603:Keratinocytes; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D011740:Pyrimidine Dimers / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011740:Pyrimidine Dimers; D051028:bcl-2-Associated X Protein; C058406:pyrimidine-pyrimidone dimer; D004247:DNA