title: Suppression of apoptosis by Bcl-2 or Bcl-xL promotes susceptibility to mutagenesis.
abstract: Bcl-2 appears to contribute to neoplasia primarily by promoting cell survival, rather than by stimulating cellular proliferation. Bcl-2, and the related protein Bcl-xL, each suppress apoptosis induced by a wide variety of stimuli in many different cell types. Here we report that suppression of apoptosis by Bcl-2 or Bcl-xL markedly elevates the levels of radiation-induced mutations. This enhanced mutagenesis is the result of an increase in mutation frequency (mutations per survivor) together with a moderate increase in viability. Ectopic expression of either Bcl-2 or Bcl-xL enhances radiation mutagenesis in cells with wtp53. Surprisingly, we found that ectopic expression of Bcl-xL also promotes mutagenesis in p53- cells. These results support the hypothesis that apoptosis plays a crucial role in maintaining genomic integrity by selectively eliminating highly mutated cells from the population.
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley 94720, USA.
authors.forename: C
authors.initials: C
authors.lastname: Cherbonnel-Lasserre
authors.forename: S
authors.initials: S
authors.lastname: Gauny
authors.forename: A
authors.initials: A
authors.lastname: Kronenberg
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology* / Q000528:radiation effects; D004249:DNA Damage; D016158:Genes, p53 / Q000502:physiology; D006801:Humans; D016296:Mutagenesis / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein