RuvC uses dynamic probing of the Holliday junction to achieve sequence specificity and efficient resolution

0518318 - BFÚ 2020 RIV GB eng J - Článek v odborném periodiku
Górecka, K. - Krepl, Miroslav - Szlachcic, A. - Poznanski, J. - Šponer, Jiří - Nowotny, M.
RuvC uses dynamic probing of the Holliday junction to achieve sequence specificity and efficient resolution.
Nature Communications. Roč. 10, SEP 10 2019 (2019), č. článku 4102. E-ISSN 2041-1723
Grant CEP: GA MŠMT EF15_003/0000477
Institucionální podpora: RVO:68081707
Klíčová slova: resolving enzyme cce1 * escherichia-coli * molecular-dynamics * crystal-structures * dna junctions * mechanism
Obor OECD: Physical chemistry
Impakt faktor: 12.121, rok: 2019
Způsob publikování: Open access
https://www.nature.com/articles/s41467-019-11900-8.pdf

Holliday junctions (HJs) are four-way DNA structures that occur in DNA repair by homologous recombination. Specialized nucleases, termed resolvases, remove (i.e., resolve) HJs. The bacterial protein RuvC is a canonical resolvase that introduces two symmetric cuts into the HJ. For complete resolution of the HJ, the two cuts need to be tightly coordinated. They are also specific for cognate DNA sequences. Using a combination of structural biology, biochemistry, and a computational approach, here we show that correct positioning of the substrate for cleavage requires conformational changes within the bound DNA. These changes involve rare high-energy states with protein-assisted base flipping that are readily accessible for the cognate DNA sequence but not for non-cognate sequences. These conformational changes and the relief of protein-induced structural tension of the DNA facilitate coordination between the two cuts. The unique DNA cleavage mechanism of RuvC demonstrates the importance of high-energy conformational states in nucleic acid readouts.
Trvalý link: http://hdl.handle.net/11104/0303487