Automated AFM analysis of DNA bending reveals initial lesion sensing strategies of DNA glycosylases
Please always quote using this URN: urn:nbn:de:bvb:20-opus-231338
- 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,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.…
Author: | Disha M. Bangalore, Hannah S. Heil, Christian F. Mehringer, Lisa Hirsch, Katharina Hemmen, Katrin G. Heinze, Ingrid Tessmer |
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URN: | urn:nbn:de:bvb:20-opus-231338 |
Document Type: | Journal article |
Faculties: | Fakultät für Biologie / Rudolf-Virchow-Zentrum |
Language: | English |
Parent Title (English): | Scientific Reports |
Year of Completion: | 2020 |
Volume: | 10 |
Article Number: | 15484 |
Source: | Scientific Reports (2020) 10:15484. https://doi.org/10.1038/s41598-020-72102-7 |
DOI: | https://doi.org/10.1038/s41598-020-72102-7 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Tag: | 8-oxoguanine; atomic-force microscopy; base pairs; crystal structure; mismatches; molecular structure; recognition; repair; structural basis; thymine |
Release Date: | 2021/04/21 |
Open-Access-Publikationsfonds / Förderzeitraum 2020 | |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |