Oxygen Metabolism Causes Chromosome Breaks and Is Associated with the Neuronal Apoptosis Observed in DNA Double-Strand Break Repair Mutants
Cells deficient in a major DNA double-strand break repair pathway (nonhomologous DNA end joining [NHEJ]) have increased spontaneous chromosome breaks [1–3]; however, the source of these chromosome breaks has remained undefined. Here, we show that the observed spontaneous chromosome breaks are partia...
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| Veröffentlicht in: | Current biology 2002-03, Vol.12 (5), p.397-402 |
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| creator | Karanjawala, Zarir E. Murphy, Niamh Hinton, David R. Hsieh, Chih-Lin Lieber, Michael R. |
| description | Cells deficient in a major DNA double-strand break repair pathway (nonhomologous DNA end joining [NHEJ]) have increased spontaneous chromosome breaks [1–3]; however, the source of these chromosome breaks has remained undefined. Here, we show that the observed spontaneous chromosome breaks are partially suppressed by reducing the cellular oxygen tension. Conversely, elevating the level of reactive oxygen species by overexpressing the antioxidant enzyme superoxide dismutase 1 (SOD1), in a transgenic mouse, increases chromosome breakage. The effect of SOD1 can also be modulated by cellular oxygen tension. The elevated chromosome breakage correlates histologically with a significant increase in the amount of neuronal cell death in Ku86−/− SOD1 transgenic embryos over that seen in Ku86−/− embryos. Therefore, oxygen metabolism is a major source of the genomic instability observed in NHEJ-deficient cells and, presumably, in all cells. |
| doi_str_mv | 10.1016/S0960-9822(02)00684-X |
| format | Article |
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Therefore, oxygen metabolism is a major source of the genomic instability observed in NHEJ-deficient cells and, presumably, in all cells.</description><subject>Animals</subject><subject>Antigens, Nuclear</subject><subject>Apoptosis</subject><subject>Cells, Cultured</subject><subject>Cerebral Cortex - cytology</subject><subject>Cerebral Cortex - embryology</subject><subject>Cerebral Cortex - metabolism</subject><subject>Chromosome Breakage</subject><subject>DNA Helicases</subject><subject>DNA Repair - genetics</subject><subject>DNA Repair - physiology</subject><subject>DNA-Binding Proteins - deficiency</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Embryonic and Fetal Development - genetics</subject><subject>Humans</subject><subject>Ku Autoantigen</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Mutation</subject><subject>Neurons - cytology</subject><subject>Neurons - metabolism</subject><subject>Nuclear Proteins - deficiency</subject><subject>Nuclear Proteins - genetics</subject><subject>Oxygen - metabolism</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Superoxide Dismutase - genetics</subject><subject>Superoxide Dismutase - metabolism</subject><subject>Superoxide Dismutase-1</subject><issn>0960-9822</issn><issn>1879-0445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAURi1ERYfCI4C8QrAItRNPYq_QMOWnUtuRKEjdWY5zwxiSOPV1Cn0GXrpOZ1SWlSxZss_3XdmHkFecveeMl8eXTJUsUzLP37L8HWOlFNnVE7LgslIZE2L5lCwekEPyHPEXYzyXqnxGDjmX6VTxBfm3-Xv7EwZ6DtHUvnPY07WZEJCut8H3Hn0P9GMA8xupGRp6inSF6K0zERr6x8UtjVugFzAFP5iOrkY_Ro8O6aZGCDcJcgM9uVjREz_VHWSXMcw995X0G4zGBXo-RTNEfEEOWtMhvNzvR-TH50_f11-zs82X0_XqLLNC8ZgJKWRVm6pZ1qy0RcXaxs5Pa6WU3BZ5zQ2oojSyym3RGsvTJdSNVS1LOWWKI_Jm1zsGfz0BRt07tNB1ZgA_oa64UEqo8lGQy6JSiosELnegDR4xQKvH4HoTbjVnetal73Xp2YVmac269FXKvd4PmOoemv-pvZ8EfNgBkP7jxkHQaB0MFhoXwEbdePfIiDt6a6ZJ</recordid><startdate>20020305</startdate><enddate>20020305</enddate><creator>Karanjawala, Zarir E.</creator><creator>Murphy, Niamh</creator><creator>Hinton, David R.</creator><creator>Hsieh, Chih-Lin</creator><creator>Lieber, Michael R.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>20020305</creationdate><title>Oxygen Metabolism Causes Chromosome Breaks and Is Associated with the Neuronal Apoptosis Observed in DNA Double-Strand Break Repair Mutants</title><author>Karanjawala, Zarir E. ; 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however, the source of these chromosome breaks has remained undefined. Here, we show that the observed spontaneous chromosome breaks are partially suppressed by reducing the cellular oxygen tension. Conversely, elevating the level of reactive oxygen species by overexpressing the antioxidant enzyme superoxide dismutase 1 (SOD1), in a transgenic mouse, increases chromosome breakage. The effect of SOD1 can also be modulated by cellular oxygen tension. The elevated chromosome breakage correlates histologically with a significant increase in the amount of neuronal cell death in Ku86−/− SOD1 transgenic embryos over that seen in Ku86−/− embryos. Therefore, oxygen metabolism is a major source of the genomic instability observed in NHEJ-deficient cells and, presumably, in all cells.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>11882291</pmid><doi>10.1016/S0960-9822(02)00684-X</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete; Cell Press Free Archives; EZB Electronic Journals Library |
| subjects | Animals Antigens, Nuclear Apoptosis Cells, Cultured Cerebral Cortex - cytology Cerebral Cortex - embryology Cerebral Cortex - metabolism Chromosome Breakage DNA Helicases DNA Repair - genetics DNA Repair - physiology DNA-Binding Proteins - deficiency DNA-Binding Proteins - genetics Embryonic and Fetal Development - genetics Humans Ku Autoantigen Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Mutation Neurons - cytology Neurons - metabolism Nuclear Proteins - deficiency Nuclear Proteins - genetics Oxygen - metabolism Reactive Oxygen Species - metabolism Superoxide Dismutase - genetics Superoxide Dismutase - metabolism Superoxide Dismutase-1 |
| title | Oxygen Metabolism Causes Chromosome Breaks and Is Associated with the Neuronal Apoptosis Observed in DNA Double-Strand Break Repair Mutants |
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