Chemical approaches toward understanding base excision DNA repair |
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Authors: | Orlando D Schä rer,Li Deng,Gregory L Verdine |
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Affiliation: | aDepartment of Cell Biology and Genetics, Erasmus University, PO Box 1738, 3000 DR Rotterdam, The Netherlands;bDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, 02138, USA |
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Abstract: | Despite the importance of DNA repair in protecting the genome, the molecular basis for damage recognition and repair remains poorly understood. In the base excision repair pathway (BER), DNA glycosylases recognize and excise damaged bases from DNA. This review focuses on the recent development of chemical approaches that have been applied to the study of BER enzymes. Several distinctive classes of noncleavable substrate analogs that form stable complexes with DNA glycosylases have recently been designed and synthesized. These analogs have been used for biochemical and structural analyses of protein—DNA complexes involving DNA glycosylases, and for the isolation of a novel DNA glycosylase. An approach to trap covalently a DNA glycosylase-intermediate complex has also been used to elucidate the mechanism of DNA glycosylases. |
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Keywords: | Abbreviations: AP abasic BER base-excision repair pathway UDG uracil DNA glycosylase |
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