Automated AFM analysis of DNA bending reveals initial lesion sensing strategies of DNA glycosylases

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 invest...

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Bibliographic Details
Published inScientific reports Vol. 10; no. 1; p. 15484
Main Authors Bangalore, Disha M., Heil, Hannah S., Mehringer, Christian F., Hirsch, Lisa, Hemmen, Katherina, Heinze, Katrin G., Tessmer, Ingrid
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 23.09.2020
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Automation - methods
DNA Damage
DNA Glycosylases - metabolism
DNA Glycosylases - physiology
DNA Repair - physiology
High-Throughput Screening Assays
Humanities and Social Sciences
Humans
Microscopy, Atomic Force - methods
multidisciplinary
Nucleic Acid Conformation
Science
Science (multidisciplinary)
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-72102-7