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Beilstein Talk - Cryo-EM in Enzymology II: Structural factors governing the fidelty of DNA recombinases RAD51 and DMC1

5 May 2021 08:00-09:00, Frankfurt am Main, Germany

Watson-Crick base pairing is the foundation for high-fidelity DNA synthesis, repair, and recombination. However, not all of these processes occur at high-fidelity in various cellular functions. The structural basis of DNA polymerases with contrasting fidelity has been investigated extensively as reviewed recently (1). Both high-fidelity and mismatch-tolerant DNA recombination, catalyzed by RAD51 and DMC1 recombinases, respectively, are indispensable for maintaining genomic integrity and generating genetic diversity. However, it remains unknown how DMC1 overcomes the Watson-Crick forces to allow for mismatched base pairing. In a recent study (2), we used cryo-EM, MD simulations, and functional assays to suggest that the recombination fidelity is governed primarily by two structural factors involving lineage-specific residues in coordination with conserved residues: flexibility of the boundary gate to the base-pair triplet, and strength of support for the DNA backbone by a structural wall. Tight gate and weak wall render high fidelity for RAD51 because mismatched base-pairs could not fit and thus destabilize the DNA backbone, whereas loose gate and strong wall confer mismatch tolerance due to the opposite effects.

Beilstein-Institut, Online Talk, Frankfurt am Main, 60487, Germany

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