Interplay Muts With Beta Clamp On Mismatched Dna

MutS, a mismatch repair initiation protein, forms a transient clamp to search for mismatched nucleotides by rotational-coupled translational diffusion while in continuous but nonspecific contact with the helical duplex DNA. When MutS encounters a mismatch, ATP binding by MutS results in an extremely stable sliding clamp that slides off the mismatch and moves along the adjacent duplex DNA driven simply by 1D thermal diffusion. The DNA mismatch repair is a timing process to be operated after DNA is newly synthesized. The β-clamp protein, a subunit of the DNA polymerase III holoenzyme, encircles duplex DNA and stably diffuses on the DNA after a lagging strand is synthesized. The long dwell time of the sliding β-clamp on DNA results in its accumulation on the lagging strand, which may obstruct the way of the translocation of MutS to find a mismatch and to transmit its finding to a downstream site. We will present how the sliding β-clamp interacts with MutS on mismatched DNA. The single-molecule studies using FRET and a single particle tracking suggest that the β-clamp increases the searching time of MutS required to locate a mismatch site through the physical interaction with MutS and is separated from MutS bound to ATP at the mismatch.