Manju Hingorani, professor of molecular biology and biochemistry, is the co-author of “MutL Traps MutS at a DNA Mismatch,” published in the July 21 issue of the Proceedings of the National Academy of Sciences (PNAS). Postdoctoral researcher Miho Sakato also co-authored the article.
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 percent of hereditary nonpolyposis colorectal cancer 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.
In this study, Hingorani, Sakato and their fellow researchers discovered that MutL fundamentally changes the properties of mismatch-bound MutS by preventing it from sliding away from the mismatch, which it normally does when isolated. This finding suggests a mechanism for localizing the activity of repair proteins near the mismatch.