Dynamic basis for one-dimensional DNA scanning by the mismatch repair complex Msh2-Msh6.
The ability of proteins to locate specific sites or structures among a vast excess of nonspecific DNA is a fundamental theme in biology. Yet the basic principles that govern these mechanisms remain poorly understood. For example, mismatch repair proteins must scan millions of base pairs to find rare biosynthetic errors, and they then must probe the surrounding region to identify the strand discrimination signals necessary to distinguish the parental and daughter strands. To determine how these proteins might function we used single-molecule optical microscopy to answer the following question: how does the mismatch repair complex Msh2-Msh6 interrogate undamaged DNA? Here we show that Msh2-Msh6 slides along DNA via one-dimensional diffusion. These findings indicate that interactions between Msh2-Msh6 and DNA are dominated by lateral movement of the protein along the helical axis and have implications for how MutS family members travel along DNA at different stages of the repair reaction.
Gorman
Jason
J
Department of Biological Sciences, Columbia University, New York, NY 10032, USA.
Chowdhury
Arindam
A
Surtees
Jennifer A
JA
Shimada
Jun
J
Reichman
David R
DR
Alani
Eric
E
Greene
Eric C
EC
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D053843:DNA Mismatch Repair; D004271:DNA, Fungal / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D008856:Microscopy, Fluorescence / Q000379:methods; D008958:Models, Molecular; D051718:MutS Homolog 2 Protein / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000502:physiology*
D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C098790:MSH6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C489751:MSH2 protein, S cerevisiae; D051718:MutS Homolog 2 Protein