Mismatch repair.
Highly conserved MutS homologs (MSH) and MutL homologs (MLH/PMS) are the fundamental components of mismatch repair (MMR). After decades of debate, it appears clear that the MSH proteins initiate MMR by recognizing a mismatch and forming multiple extremely stable ATP-bound sliding clamps that diffuse without hydrolysis along the adjacent DNA. The function(s) of MLH/PMS proteins is less clear, although they too bind ATP and are targeted to MMR by MSH sliding clamps. Structural analysis combined with recent real-time single molecule and cellular imaging technologies are providing new and detailed insight into the thermal-driven motions that animate the complete MMR mechanism.
From the Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Wexner Medical Center, Columbus, Ohio 43210 and the Department of Physics and the Biophysics Program, The Ohio State University, Columbus, Ohio 43210 rfishel@osu.edu.
Richard
R
Fishel
D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D053843:DNA Mismatch Repair / Q000502:physiology*; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*
D009687:Nuclear Proteins; D000255:Adenosine Triphosphate; D004247:DNA; D045643:DNA Repair Enzymes
DNA mismatch repair; DNA repair; Lynch syndrome; cancer biology; hMLH1; hMSH2; hereditary non-polyposis colorectal cancer; mutagenesis; single molecule analysis; single-molecule biophysics