Werner and Bloom helicases are involved in DNA repair in a complementary fashion

• Published in: Oncogene Vol. 21; no. 6; pp. 954 - 963
• Main Authors: IMAMURA, Osamu, FUJITA, Kumiko, ITOH, Chie, TAKEDA, Shunichi, FURUICHI, Yasuhiro, MATSUMOTO, Takehisa
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 31.01.2002; Nature Publishing Group
• Subjects: 4-Nitroquinoline 1-oxide; 4-Nitroquinoline-1-oxide - pharmacology; Adenosine Triphosphatases - deficiency; Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - physiology; Amino Acid Sequence; Animals; B-Lymphocytes - drug effects; B-Lymphocytes - radiation effects; B-Lymphocytes - ultrastructure; Biological and medical sciences; Bloom Syndrome - enzymology; Bloom Syndrome - genetics; Bloom's syndrome; Camptothecin; Camptothecin - pharmacology; Cell Cycle; Cell Line; Chickens; Chromosome Aberrations; Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...); Clone Cells - drug effects; Clone Cells - metabolism; Coculture Techniques; Deoxyribonucleic acid; DNA; DNA - drug effects; DNA - radiation effects; DNA Damage; DNA helicase; DNA Helicases - deficiency; DNA Helicases - genetics; DNA Helicases - physiology; DNA repair; DNA Repair - physiology; Drug Resistance; Etoposide - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Targeting; Genes. Genome; Genetic aspects; Genomic instability; Genotoxicity; Hereditary diseases; Humans; Hypersensitivity; Immunodeficiency; Integration; Lymphocytes B; Medical genetics; Medical sciences; Methyl methanesulfonate; Methyl Methanesulfonate - pharmacology; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Mutagenesis. Repair; Mutagenicity Tests; Mutants; Oncogenes; Physiological aspects; Radiation Tolerance; RecQ Helicases; RecQ protein; Senescence; Sequence Alignment; Sequence Homology, Amino Acid; Sister chromatid exchange; Sister Chromatid Exchange - drug effects; Species Specificity; Tumorigenesis; Ultraviolet Rays; Werner syndrome; Werner Syndrome - enzymology; Werner Syndrome - genetics; Werner's syndrome; Japan; Double strand break; Bloom syndrome; Base mismatching; Excision; Predisposition; Lesion; Werner syndrome; Repair
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1205143

Werner syndrome (WS) is a recessive disorder characterized by premature senescence. Bloom syndrome (BS) is a recessive disorder characterized by short stature and immunodeficiency. A common characteristic of both syndromes is genomic instability leading to tumorigenesis. WRN and BLM genes causing WS and BS, encode proteins that are closely related to the RecQ helicase. We produced WRN-/-, BLM-/- and WRN(-/-)/BLM(-/-) mutants in the chicken B-cell line DT40. WRN-/- cells showed hypersensitivities to genotoxic agents, such as 4-nitroquinoline 1-oxide, camptothecin and methyl methanesulfonate. They also showed a threefold increase in targeted integration rate of exogenous DNAs, but not in sister chromatid exchange (SCE) frequency. BLM-/- cells showed hypersensitivities to the genotoxic agents as well as ultraviolet (UV) light, in addition to a 10-fold increase in targeted integration rate and an 11-fold increase in SCE frequency. In WRN(-/-)/BLM(-/-) cells, synergistically increased hypersensitivities to the genotoxic agents were observed whereas both SCE frequencies and targeted integration rates were partially diminished compared to the single mutants. Chromosomal aberrations were also synergistically increased in WRN(-/-)/BLM(-/-) cells when irradiated with UV light in late S to G(2) phases. These results suggest that both WRN and BLM may be involved in DNA repair in a complementary fashion.