Resolving the subtle details of human DNA alkyltransferase lesion search and repair mechanism by single-molecule studies.
Proc Natl Acad Sci U S A
; 119(11): e2116218119, 2022 03 15.
Article
em En
| MEDLINE
| ID: mdl-35259021
ABSTRACT
SignificanceWe directly visualize DNA translocation and lesion recognition by the O6-alkylguanine DNA alkyltransferase (AGT). Our data show bidirectional movement of AGT monomers and clusters on undamaged DNA that depended on Zn2+ 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.
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Base de dados:
MEDLINE
Assunto principal:
DNA
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Alquil e Aril Transferases
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Reparo do DNA
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Imagem Individual de Molécula
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article