Beta clamp directs localization of mismatch repair in Bacillus subtilis.
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.
Simmons
Lyle A
LA
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Davies
Bryan W
BW
Grossman
Alan D
AD
Walker
Graham C
GC
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000235:genetics*; D020137:Base Pair Mismatch; D053843:DNA Mismatch Repair; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051719:MutS DNA Mismatch-Binding Protein / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D009154:Mutation
D049452:Green Fluorescent Proteins; D051719:MutS DNA Mismatch-Binding Protein