Phenotypic heterogeneity within the first complementation group of UV-sensitive mutants of Chinese hamster cell lines |
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| Affiliation: | 1. Department of Radiation Genetics and Chemical Mutagenesis, State University of Leidin, Leiden, The Netherlands;2. TNO Medical Biological Laboratory, Rijswijk, The Netherlands;3. Department of Cell Biology and Genetics, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands;4. J.A. Cohen Institute, Interuniversity Research Institute for Radioapathology and Radiation Protection, Leiden The Netherlands;1. Institute of Optical Materials and Chemical Biology, School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, PR China;2. Institute of Fluorescent Probes for Biological Imaging, School of Chemistry and Chemical Engineering, School of Materials Science and Engineering, University of Jinan, Jinan, Shandong, 250022, PR China;1. Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI;2. Department of Surgery, University of Michigan, Ann Arbor, MI;3. Wayne State University Medical School, Detroit, MI;1. Department of Medicine, Division of Translational Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA;2. Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA;3. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;4. Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA;3. Department of Biochemistry and Molecular Biology, University of Nevada School of Medicine, Reno, Nevada 89557;4. the Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520;5. the School of Mathematics and Statistics, University of New South Wales, Sydney, New South Wales 2052, Australia;1. Laboratoire Plasma et Conversion d’Énergie (LAPLACE), UMR 5213 CNRS-INPT-UPS, 2, rue Charles Camichel, 31071 Toulouse, France;2. ONERA - System Control and Flight Dynamics Department, 2 av. Edouard Belin, 31055 Toulouse, France;3. Institut de Mécanique des Fluides de Toulouse (IMFT), UMR 5502 CNRS-INPT-UPS, Allée du prof. Camille Soula, 31400 Toulouse, France;4. Massachusetts Institute of Technology (MIT), 77 Massachusetts Ave, Cambridge, MA 02139, United States;1. Cellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA;2. Medical Scientist Training Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA;3. Department of Molecular Genetics, Oncode Institute, Erasmus Medical Center, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 CN Rotterdam, the Netherlands;4. Department of Clinical Genetics, Erasmus Medical Center, University Medical Center, 3015 GD Rotterdam, the Netherlands;5. Undiagnosed Diseases Program and Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA;6. Department of Biochemistry and Molecular Biochemistry, Thomas Jefferson University, Philadelphia, PA 19107, USA;7. Metabolic Unit, Department of Clinical Chemistry, Amsterdam University Medical Center and Amsterdam Gastroenterology and Metabolism, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, 1081 HZ Amsterdam, the Netherlands;8. Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA;9. Department of Neurology, University of Michigan Medical School, Ann Arbor, MI 48109, USA;10. Genetic Metabolic Diseases, Amsterdam University Medical Center, University of Amsterdam, 1081 HZ Amsterdam, the Netherlands |
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| Abstract: | A DNA-repair mutant was characterized that has the extraordinary and interesting properties of extreme sensitivity to UV killing combined with a high level of nucleotide excision repair. The mutant V-H1 isolated from the V79 Chinese hamster cell line appeared very stable, with a reversion frequency of about 3.5 × 10−7. Genetic complementation analysis indicates that V-H1 belongs to the first complementation group of UV-sensitive Chinese hamster ovary (CHO) mutants described by Thompson et al. (1981). This correponds with data on cross-sensitivity and mutation induction after UV irradiation published by this group. Surprisingly, the mutant V-H1 shows only slightly reduced (to ∼ 70%) unscheduled DNA synthesis (UDS) after UV exposure, while the other two mutants of this complementation group are deficient in UDS after UV. In agreement with the high residual UDS, in V-H1 also the amount of repair replication in response to UV treatment is relatively high (∼ 50%). It has also been shown that the incision step of the nucleotide excision pathway takes place in V-H1 (with a lower rate than observed in wild-type cells), whereas another mutant (UV5) of the same complementation group is deficient in incision.This heterogeneity within the first complementation group indicates that the repair gene of this complementation group may have more than one functionally domain or that the gene is not involved in the incision per se but is involved in e.g. preferential repair of active genes. |
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