Base excision repair in chromatin: Insights from reconstituted systems |
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| Affiliation: | 3. Université Paris Sud, Institute of Molecular and Cellular Biochemistry and Biophysics, UMR 8619, 91405 Orsay, France,;4. CNRS, 91405 Orsay, France, and;5. Department of Virology, Institut Pasteur, Pathogenesis of Hepatitis B Virus, 75015 Paris, France;3. Departments of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701;4. Biological Sciences, University of Arkansas, Fayetteville, Arkansas 72701;1. Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota Cancer Center, Minneapolis, MN;;2. Department of Hematology and Oncology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany;;3. Departments of Infectious Diseases and Immunology, St. Jude Children''s Research Hospital, Memphis, TN;;4. Blood and Marrow Transplant Program, Division of Hematology, Oncology and Transplantation, University of Minnesota Cancer Center, Minneapolis, MN;;5. Cancer Center and Department of Pediatrics, Georgia Regent''s University, Augusta, GA;;6. Departments of Dermatology and Internal Medicine, School of Medicine, University of California, Davis, Sacramento, CA;;7. Lineberger Comprehensive Cancer Center, Inflammatory Diseases Institute, Departments of Genetics and Microbiology and Immunology, University of North Carolina, Chapel Hill, NC;;8. The Wistar Institute, Philadelphia, PA;;9. Dipartimento di afferenza Medicina, Verona University, Verona, Italy; and;10. Centre for Biological Signaling Studies BIOSS, Freiburg, Germany;1. Research Center for Drug Discovery Technology, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, Korea;2. Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea;3. Department of Functional Genomics, University of Science and Technology, Daejeon, Korea;1. Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, 02912, United States;2. Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, 21201, United States;3. University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD, 21201, United States;4. Department of Chemistry, Brown University, Providence, RI, 02912, United States |
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| Abstract: | The process of base excision repair has been completely reconstituted in vitro and structural and biochemical properties of the component enzymes thoroughly studied on naked DNA templates. More recent work in this field aims to understand how BER operates on the natural substrate, chromatin [1], [2]. Toward this end, a number of researchers, including the Smerdon group, have focused attention to understand how individual enzymes and reconstituted BER operate on nucleosome substrates. While nucleosomes were once thought to completely restrict access of DNA-dependent factors, the surprising finding from these studies suggests that at least some BER components can utilize target DNA bound within nucleosomes as substrates for their enzymatic processes. This data correlates well with both structural studies of these enzymes and our developing understanding of nucleosome conformation and dynamics. While more needs to be learned, these studies highlight the utility of reconstituted BER and chromatin systems to inform our understanding of in vivo biological processes. |
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| Keywords: | Base excision repair Long-patch (LP) BER Short-patch (SP) BER Nucleosomes Chromatin Histones |
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