Differential inhibitors of DNA polymerases alpha and delta |
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| Authors: | J J Byrnes |
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| Affiliation: | 1. Veterans Administration Medical Center 1201 N.W. 16th Street, Miami, FL 33125 USA;2. The Center for Blood Diseases University of Miami School of Medicine, Miami, FL, USA;1. Department of Anatomy, Histology and Embryology, MOE Key Laboratory of Carcinogenesis and Translational Research, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing, 100191, China;2. MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, 100084, China;3. CAS Key Laboratory of Bio-medical Diagnostic, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China;1. Howard Hughes Medical Institute and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA;2. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA;3. Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK;4. Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK;5. Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK;1. Department of Radiation Oncology, The Ohio State University, Columbus, OH, 43210, USA;2. Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA;1. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA;2. Department of Medicine (Hematology, Oncology), Vanderbilt University School of Medicine, Nashville, TN 37232, USA;3. VA Tennessee Valley Healthcare System, Nashville, TN 37212, USA |
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| Abstract: | DNA polymerases alpha and delta from bone marrow are similar in many respects, the major known difference being the exonuclease activity of delta. Differential inhibitors of alpha and delta have been sought to assist in their functional and physical separation. Butylphenyl deoxyguanosine triphosphate is one. It effectively inhibits alpha at less than 1 microM concentration, whereas more than 100 microM is required to similarly inhibit delta. Another is the monoclonal antibody, SJK 132-20, which neutralizes the polymerase activity of alpha but not delta. These differential inhibitors further define alpha and delta as separate categories of eukaryotic DNA polymerase and promise to facilitate the study of both. |
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