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

Bangalore, Disha M ; Heil, Hannah S LU orcid ; Mehringer, Christian F ; Hirsch, Lisa ; Hemmen, Katherina ; Heinze, Katrin G and Tessmer, Ingrid (2020) In Scientific Reports 10. p.1-15
Abstract

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... (More)

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.

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author
; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Automation/methods, DNA Damage, DNA Glycosylases/metabolism, DNA Repair/physiology, High-Throughput Screening Assays, Humans, Microscopy, Atomic Force/methods, Nucleic Acid Conformation
in
Scientific Reports
volume
10
article number
15484
pages
1 - 15
publisher
Nature Publishing Group
external identifiers
  • pmid:32968112
  • scopus:85091355294
ISSN
2045-2322
DOI
10.1038/s41598-020-72102-7
language
English
LU publication?
no
id
87f3355e-f5fa-4ba0-95d1-1166d83f60af
date added to LUP
2025-04-26 12:10:17
date last changed
2025-07-06 18:15:01
@article{87f3355e-f5fa-4ba0-95d1-1166d83f60af,
  abstract     = {{<p>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.</p>}},
  author       = {{Bangalore, Disha M and Heil, Hannah S and Mehringer, Christian F and Hirsch, Lisa and Hemmen, Katherina and Heinze, Katrin G and Tessmer, Ingrid}},
  issn         = {{2045-2322}},
  keywords     = {{Automation/methods; DNA Damage; DNA Glycosylases/metabolism; DNA Repair/physiology; High-Throughput Screening Assays; Humans; Microscopy, Atomic Force/methods; Nucleic Acid Conformation}},
  language     = {{eng}},
  month        = {{09}},
  pages        = {{1--15}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Automated AFM analysis of DNA bending reveals initial lesion sensing strategies of DNA glycosylases}},
  url          = {{http://dx.doi.org/10.1038/s41598-020-72102-7}},
  doi          = {{10.1038/s41598-020-72102-7}},
  volume       = {{10}},
  year         = {{2020}},
}