Automated AFM analysis of DNA bending reveals initial lesion sensing strategies of DNA glycosylases
| Autor: | Disha M. Bangalore, Hannah S. Heil, Christian F. Mehringer, Lisa Hirsch, Katherina Hemmen, Katrin G. Heinze, Ingrid Tessmer |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
DNA Repair
lcsh:Medicine Imaging techniques Microscopy Atomic Force Characterization and analytical techniques Article DNA Glycosylases Techniques and instrumentation Automation Atomic force microscopy Nanoscience and technology Biophysical chemistry ddc:570 Humans DNA nanotechnology lcsh:Science Microscopy lcsh:R Proteins Nanobiotechnology DNA Molecular conformation High-Throughput Screening Assays Enzymes Enzyme mechanisms Nucleic Acid Conformation lcsh:Q Structural biology DNA Damage |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-15 (2020) |
| Popis: | Base excision repair is the dominant DNA repair pathway of chemical modifications such as deamination, oxidation, or alkylation of DNA bases, which endanger genome integrity due to their high mutagenic potential. Detection and excision of these base lesions is achieved by DNA glycosylases. To investigate the remarkably high efficiency in target site search and recognition by these enzymes, we applied single molecule atomic force microscopy (AFM) imaging to a range of glycosylases with structurally different target lesions. Using a novel, automated, unbiased, high-throughput analysis approach, we were able to resolve subtly different conformational states of these glycosylases during DNA lesion search. Our results lend support to a model of enhanced lesion search efficiency through initial lesion detection based on altered mechanical properties at lesions. Furthermore, its enhanced sensitivity and easy applicability also to other systems recommend our novel analysis tool for investigations of diverse, fundamental biological interactions. |
| Databáze: | OpenAIRE |
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