6s16
From Proteopedia
T. thermophilus RuvC in complex with Holliday junction substrate
Structural highlights
FunctionRUVC_THET8 Nuclease that resolves Holliday junction intermediates in genetic recombination. Cleaves the cruciform structure in supercoiled DNA by nicking to strands with the same polarity at sites symmetrically opposed at the junction in the homologous arms and leaves a 5'-terminal phosphate and a 3'-terminal hydroxyl group (By similarity). Publication Abstract from PubMedHolliday 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. RuvC uses dynamic probing of the Holliday junction to achieve sequence specificity and efficient resolution.,Gorecka KM, Krepl M, Szlachcic A, Poznanski J, Sponer J, Nowotny M Nat Commun. 2019 Sep 10;10(1):4102. doi: 10.1038/s41467-019-11900-8. PMID:31506434[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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