Simmons Lyle A, Davies Bryan W, Grossman Alan D, Walker Graham C
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Mol Cell. 2008 Feb 15;29(3):291-301. doi: 10.1016/j.molcel.2007.10.036.
MutS homologs function in several cellular pathways including mismatch repair (MMR), the process by which mismatches introduced during DNA replication are corrected. We demonstrate that the C terminus of Bacillus subtilis MutS is necessary for an interaction with beta clamp. This interaction is required for MutS-GFP focus formation in response to mismatches. Reciprocally, we show that a mutant of the beta clamp causes elevated mutation frequencies and is reduced for MutS-GFP focus formation. MutS mutants defective for interaction with beta clamp failed to support the next step of MMR, MutL-GFP focus formation. We conclude that the interaction between MutS and beta is the major molecular interaction facilitating focus formation and that beta clamp aids in the stabilization of MutS at a mismatch in vivo. The striking ability of the MutS C terminus to direct focus formation at replisomes by itself, suggests that it is mismatch recognition that licenses MutS's interaction with beta clamp.
MutS同源物在包括错配修复（MMR）在内的多种细胞途径中发挥作用，错配修复是纠正DNA复制过程中引入的错配的过程。我们证明枯草芽孢杆菌MutS的C末端对于与β钳的相互作用是必需的。这种相互作用是响应错配时MutS-GFP焦点形成所必需的。相反，我们表明β钳的突变体导致突变频率升高，并且MutS-GFP焦点形成减少。与β钳相互作用有缺陷的MutS突变体无法支持MMR的下一步，即MutL-GFP焦点形成。我们得出结论，MutS与β之间的相互作用是促进焦点形成的主要分子相互作用，并且β钳有助于在体内错配处稳定MutS。MutS C末端自身在复制体处直接形成焦点的惊人能力表明，是错配识别许可了MutS与β钳的相互作用。
