Resolving the subtle details of human DNA alkyltransferase lesion search and repair mechanism by single-molecule studies.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35259021.
- Also identified by DOI 10.1073/pnas.2116218119 and PMC identifier 8931253.
- Licence recorded as CC BY-NC-ND.
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Abstract
SignificanceWe directly visualize DNA translocation and lesion recognition by the O<sup>6</sup>-alkylguanine DNA alkyltransferase (AGT). Our data show bidirectional movement of AGT monomers and clusters on undamaged DNA that depended on Zn<sup>2+</sup> occupancy of AGT. A role of cooperative AGT clusters in enhancing lesion search efficiencies by AGT has previously been proposed. Surprisingly, our data show no enhancement of DNA translocation speed by AGT cluster formation, suggesting that AGT clusters may serve a different role in AGT function. Our data support preferential cluster formation by AGT at alkyl lesions, suggesting a role of these clusters in stabilizing lesion-bound complexes. From our data, we derive a new model for the lesion search and repair mechanism of AGT.
Medical subject headings
- Alkyl and Aryl Transferases
- DNA
- DNA Repair
- Single Molecule Imaging