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Dynamics and Mechanism of DNA-Bending Proteins in Binding Site Recognition

Monday, March 19, 2PM – 3PM
ACE 6.304

Anjum Ansari

How DNA-bending proteins recognize their specific binding sites on DNA remains unclear, especially for those proteins that use “indirect readout”, in which sequence-dependent variations in DNA flexibility are key to the recognition mechanism. The question remains as to whether the protein bends the DNA (protein-induced bending) or, alternatively, “prebent” DNA conformations are thermally accessible, which the protein captures to form the specific complex (conformational capture). To distinguish between these mechanisms requires characterization of reaction intermediates, and, in particular, snapshots of the transition state along the recognition pathway. I will present such a snapshot, from time-resolved measurements of DNA bending dynamics in complex with IHF, an architectural protein from E. coli that recognizes several sites on phage λ DNA, and bends its cognate sites in a sharp U-turn. I will also present more recent work on DNA bending/base-flipping dynamics within a 3-nucleotide mismatched bubble that mimics a UV-induced lesion recognized by XPC/Rad4, a DNA damage recognition protein that plays a critical role in the repair machinery.

*Refreshments served at 1:45 PM

Hosted by Ron Elber