Non-flipping DNA glycosylase AlkD scans DNA without formation of a stable interrogation complex
| Autor: | Pernille Blicher, Katharina Till, Robin Diekmann, Kyrre Glette, Mark Schüttpelz, Paul Hoff Backe, Magnar Bjørås, Jim Torresen, Bjørn Dalhus, Alexander D. Rowe, Arash Ahmadi |
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| Rok vydání: | 2021 |
| Předmět: |
DNA
Bacterial QH301-705.5 Mutant Medicine (miscellaneous) Article General Biochemistry Genetics and Molecular Biology DNA Glycosylases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Bacterial Proteins Single-molecule biophysics Biophysical chemistry Biology (General) 030304 developmental biology Base excision repair chemistry.chemical_classification 0303 health sciences Repair enzymes Enzyme chemistry DNA glycosylase Helix Biophysics General Agricultural and Biological Sciences 030217 neurology & neurosurgery DNA |
| Zdroj: | Communications Biology, Vol 4, Iss 1, Pp 1-8 (2021) Communications Biology |
| ISSN: | 2399-3642 |
| Popis: | The multi-step base excision repair (BER) pathway is initiated by a set of enzymes, known as DNA glycosylases, able to scan DNA and detect modified bases among a vast number of normal bases. While DNA glycosylases in the BER pathway generally bend the DNA and flip damaged bases into lesion specific pockets, the HEAT-like repeat DNA glycosylase AlkD detects and excises bases without sequestering the base from the DNA helix. We show by single-molecule tracking experiments that AlkD scans DNA without forming a stable interrogation complex. This contrasts with previously studied repair enzymes that need to flip bases into lesion-recognition pockets and form stable interrogation complexes. Moreover, we show by design of a loss-of-function mutant that the bimodality in scanning observed for the structural homologue AlkF is due to a key structural differentiator between AlkD and AlkF; a positively charged β-hairpin able to protrude into the major groove of DNA. Ahmadi et al. use a single-molecule tracking method to describe the DNA scanning mode of AlkD, a HEAT-like repeat DNA glycosylase. They show that, contrary to other glycosylases that use a base-flipping mechanism, AlkD scans the DNA without forming a stable interrogation complex. |
| Databáze: | OpenAIRE |
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