Single-molecule imaging reveals target-search mechanisms during DNA mismatch repair

• DOI: 10.1073/pnas.1211364109
• Publication Date: 2012-09-25T10:48:49Z
• Authors: Jason Gorman; Feng Wang; Sy Redding; Aaron J. Plys; Teresa Fazio; Shalom Wind; Eric E. Alani; Eric C. Greene
• Keywords: Protein Stability; DNA; DNA Mismatch Repair; Models, Biological; MutS DNA Mismatch-Binding Protein; Substrate Specificity; Diffusion; Protein Transport; Adenosine Triphosphate; DNA Repair Enzymes; Imaging, Three-Dimensional; MutL Proteins; Humans; Protein Binding

The ability of proteins to locate specific targets among a vast excess nonspecific DNA is fundamental theme in biology. Basic principles governing these search mechanisms remain poorly understood, and no study has provided direct visualization single searching for engaging target sites. Here we use the postreplicative mismatch repair MutSα MutLα as model systems understanding diffusion-based searches. Using single-molecule microscopy, directly visualize it searches lesions, lesion-bound MutSα, MutSα/MutLα complex scans flanking DNA. We also show that undergoes intersite transfer between juxtaposed segments while but this activity suppressed upon association with ensuring MutS/MutL remains associated damage-bearing strand scanning Our findings highlight hierarchy lesion- ATP-dependent transitions involving both MutLα, help establish how different modes diffusion can be used during recognition damaged