DNA mismatch repair is the process by which errors generated during DNA replication are corrected.
Mutations in the proteins that initiate mismatch repair, MutS and MutL, are associated with greater than 80% of hereditary nonpolyposis colorectal cancer (HNPCC) and many sporadic cancers.
The assembly of MutS and MutL at a mismatch is an essential step for initiating repair; however, the nature of these interactions is poorly understood.
Using single molecule fluorescence methods, which allowed the researchers to watch one protein moving on one piece of DNA at a time, they determined that when MutS finds an error, it changes shape in a way that allows MutL to bind with it, holding it in place at the site of the mismatch and preventing it from sliding away from the mismatch, which it normally does when isolated.
MutL then changes its shape to “grab” another MutL, and so on, coating the defective part of the strand and nicking the area that needs repair.
This finding suggests a mechanism for localizing the activity of repair proteins near the mismatch.