Extracts of proliferating and non-proliferating human cells display different base excision pathways and repair fidelity |
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Authors: | Mansour Akbari Javier Peña-Diaz Sonja Andersen Nina-Beate Liabakk Marit Otterlei Hans Einar Krokan |
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Institution: | 1. Center for Healthy Aging, SUND, University of Copenhagen, Denmark;2. Laboratory of Molecular Gerontology, National Institute on Aging, 251 Bayview Boulevard, Baltimore, USA;1. Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United States;2. Immunology Institute, Department of Medicine, Mount Sinai School of Medicine, New York, NY, United States;3. Oncology Program, University of Maryland Greenebaum Cancer Center, Baltimore, MD, United States;4. Department of Food and Nutrition, Seoul National University, Seoul, Republic of Korea;5. Institute for Cancer Genetics, Columbia University College of Physicians and Surgeons, New York, NY, United States;6. Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY, United States;3. Department of Biology, University of Padova, 35131 Padova, Italy;4. CRIBI Biotechnology Centre, University of Padova, 35131 Padova, Italy;5. MicroScoBio Research Center, Department of Experimental Medicine, University of Genova, 16132 Genova, Italy;12. Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy;6. Experimental Imaging Center, San Raffaele Scientific Institute, 20132 Milano, Italy;1. Laboratory of Molecular Gerontology, National Institute on Aging, NIH, Baltimore, MD 21224, USA;2. Center for Healthy Aging, SUND, University of Copenhagen, Denmark |
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Abstract: | Base excision repair (BER) of damaged or inappropriate bases in DNA has been reported to take place by single nucleotide insertion or through incorporation of several nucleotides, termed short-patch and long-patch repair, respectively. We found that extracts from proliferating and non-proliferating cells both had capacity for single- and two-nucleotide insertion BER activity. However, patch size longer than two nucleotides was only detected in extracts from proliferating cells. Relative to extracts from proliferating cells, extracts from non-proliferating cells had approximately two-fold higher concentration of POLβ, which contributed to most of two-nucleotide insertion BER. In contrast, two-nucleotide insertion in extracts from proliferating cells was not dependent on POLβ. BER fidelity was two- to three-fold lower in extracts from the non-proliferating compared with extracts of proliferating cells. Furthermore, although one-nucleotide deletion was the predominant type of repair error in both extracts, the pattern of repair errors was somewhat different. These results establish two-nucleotide patch BER as a distinct POLβ-dependent mechanism in non-proliferating cells and demonstrate that BER fidelity is lower in extracts from non-proliferating as compared with proliferating cells. |
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