Thumb-domain dynamics modulate the functional repertoire of DNA-Polymerase IV (DinB)

Author:

Okeke Damasus C12,Lidman Jens12,Matečko-Burmann Irena13,Burmann Björn M12ORCID

Affiliation:

1. Department of Chemistry and Molecular Biology, University of Gothenburg , 405 30  Göteborg , Sweden

2. Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg , 405 30  Göteborg , Sweden

3. Department of Psychiatry and Neurochemistry, University of Gothenburg , 405 30  Göteborg , Sweden

Abstract

Abstract In order to cope with the risk of stress-induced mutagenesis, cells in all kingdoms of life employ Y-family DNA polymerases to resolve resulting DNA lesions and thus maintaining the integrity of the genome. In Escherichia coli, the DNA polymerase IV, or DinB, plays this crucial role in coping with these type of mutations via the so-called translesion DNA synthesis. Despite the availability of several high-resolution crystal structures, important aspects of the functional repertoire of DinB remain elusive. In this study, we use advanced solution NMR spectroscopy methods in combination with biophysical characterization to elucidate the crucial role of the Thumb domain within DinB’s functional cycle. We find that the inherent dynamics of this domain guide the recognition of double-stranded (ds) DNA buried within the interior of the DinB domain arrangement and trigger allosteric signals through the DinB protein. Subsequently, we characterized the RNA polymerase interaction with DinB, revealing an extended outside surface of DinB and thus not mutually excluding the DNA interaction. Altogether the obtained results lead to a refined model of the functional repertoire of DinB within the translesion DNA synthesis pathway.

Funder

Swedish Research Council

Knut och Alice Wallenberg Foundation

Wallenberg Academy Fellowship

University of Gothenburg

NMRbox: National Center for Biomolecular NMR Data Processing and Analysis, a Biomedical Technology Research Resource

NIH

Swedish Universities

Publisher

Oxford University Press (OUP)

Subject

Genetics

Reference71 articles.

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