A combined structural and biochemical approach reveals translocation and stalling of UvrB on the DNA lesion as a mechanism of damage verification in bacterial nucleotide excision repair
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Title |
A combined structural and biochemical approach reveals translocation and stalling of UvrB on the DNA lesion as a mechanism of damage verification in bacterial nucleotide excision repair
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Creator |
Jaciuk, Marcin
Swuec, Paolo Gaur, Vineet Kasprzak, Joanna M. Renault, Ludovic Dobrychłop, Mateusz Nirwal, Shivlee Bujnicki, Janusz M. Costa, Alessandro Nowotny, Marcin |
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Subject |
Prokaryotic nucleotide excision repair
UvrA UvrB UvrC DNA repair |
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Description |
Accepted date: 1 November 2019
Nucleotide excision repair (NER) is a DNA repair pathway present in all domains of life. In bacteria, UvrA protein localizes the DNA lesion, followed by verification by UvrB helicase and excision by UvrC double nuclease. UvrA senses deformations and flexibility of the DNA duplex without precisely localizing the lesion in the damaged strand, an element essential for proper NER. Using a combination of techniques, we elucidate the mechanism of the damage verification step in bacterial NER. UvrA dimer recruits two UvrB molecules to its two sides. Each of the two UvrB molecules clamps a different DNA strand using its β-hairpin element. Both UvrB molecules then translocate to the lesion, and UvrA dissociates. The UvrB molecule that clamps the damaged strand gets stalled at the lesion to recruit UvrC. This mechanism allows UvrB to verify the DNA damage and identify its precise location triggering subsequent steps in the NER pathway. This work was supported by European Research Council Grants (81500 to M.N. and 261351 to J.M.B.) and the Francis Crick Institute (A.C.), which receives its core funding from Cancer Research UK (FC001065), the UK Medical Research Council (FC001065) and the Wellcome Trust (FC001065). This work was also supported by the Centre for Preclinical Research and Technology (European Union POIG.02.02.00-14-024/08-00). M.N. and J.M.B were recipients of Ideas for Poland awards from the Foundation for Polish Science. M.D. was supported by the KNOW Poznan RNA Centre (01/KNOW2/2014). We thank Life Science Editors for editing assistance. We thank Paweł Zawadzki for critically reading the manuscript and Iwona Ptasiewicz for excellent technical assistance. |
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Date |
2020-02-28T05:44:47Z
2020-02-28T05:44:47Z 2020 |
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Type |
Article
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Identifier |
DNA Repair, 85: 102746
1568-7864 https://doi.org/10.1016/j.dnarep.2019.102746 https://www.sciencedirect.com/science/article/pii/S156878641930223X?via%3Dihub http://223.31.159.10:8080/jspui/handle/123456789/1044 |
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Language |
en_US
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Format |
application/pdf
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Publisher |
Elsevier B.V.
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