Chromosomal aberrations in PARP −/− mice: Genome stabilization in immortalized cells by reintroduction of poly(ADP-ribose) polymerase cDNA
| Autor: | Zoë Weaver, Thomas Ried, RuiBai Luo, Hannah M. Young, Zhao-Qi Wang, Allen E. Coleman, Cynthia M. Simbulan-Rosenthal, Bassem R. Haddad, Mark E. Smulson, Dean S. Rosenthal |
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| Rok vydání: | 1999 |
| Předmět: |
Genome instability
DNA Complementary Tumor suppressor gene Poly ADP ribose polymerase Biology Transfection Gene Expression Regulation Enzymologic Mice Genes jun Complementary DNA Animals Genes Retinoblastoma Cell Line Transformed Chromosome Aberrations Mice Knockout Genome Multidisciplinary Oncogene Oncogene JUN Nucleic Acid Hybridization Biological Sciences Genes p53 Molecular biology Mice Inbred C57BL Female Poly(ADP-ribose) Polymerases Comparative genomic hybridization |
| Zdroj: | Proceedings of the National Academy of Sciences. 96:13191-13196 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.96.23.13191 |
| Popis: | Depletion of poly(ADP-ribose) polymerase (PARP) increases the frequency of recombination, gene amplification, sister chromatid exchanges, and micronuclei formation in cells exposed to genotoxic agents, implicating PARP in the maintenance of genomic stability. Flow cytometric analysis now has revealed an unstable tetraploid population in immortalized fibroblasts derived from PARP −/− mice. Comparative genomic hybridization detected partial chromosomal gains in 4C5-ter, 5F-ter, and 14A1-C1 in PARP −/− mice and immortalized PARP −/− fibroblasts. Neither the chromosomal gains nor the tetraploid population were apparent in PARP −/− cells stably transfected with PARP cDNA [PARP −/− (+PARP)], indicating negative selection of cells with these genetic aberrations after reintroduction of PARP cDNA. Although the tumor suppressor p53 was not detectable in PARP −/− cells, p53 expression was partially restored in PARP −/− (+PARP) cells. Loss of 14D3-ter that encompasses the tumor suppressor gene Rb-1 in PARP −/− mice was associated with a reduction in retinoblastoma(Rb) expression; increased expression of the oncogene Jun was correlated with a gain in 4C5-ter that harbors this oncogene. These results further implicate PARP in the maintenance of genomic stability and suggest that altered expression of p53, Rb, and Jun, as well as undoubtedly many other proteins may be a result of genomic instability associated with PARP deficiency. |
| Databáze: | OpenAIRE |
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