Mismatch repair protein hMSH2–hMSH6 recognizes mismatches and forms sliding clamps within a D-loop recombination intermediate
Copyright policy )Mismatch repair protein hMSH2–hMSH6 recognizes mismatches and forms sliding clamps within a D-loop recombination intermediate
Significance Recombination between divergent DNA sequences (homeologous recombination) is generally suppressed to preserve cellular genetic integrity and to ultimately introduce genetic barriers between species. Decades of genetic and cell biology studies have identified the involvement of the mismatch repair (MMR) machinery in the quality control of homologous recombination. However, the molecular mechanism by which this remarkable control is achieved is unknown. Here, we report the biophysical reconstitution and analysis of the early steps in the rejection of divergent DNA sequences by the MMR machinery during recombination initiation. We have determined that the first responder of MMR, human MutS-homolog hMSH2–hMSH6, efficiently recognizes mismatches within a D-loop recombination initiation intermediate, even in the presence of recombination initiation proteins HsRAD51 and human replication protein A (HsRPA).
- University of Illinois at Urbana–Champaign United States
- University of Illinois at Urbana Champaign United States
- The Ohio State University Wexner Medical Center United States
- University of Iowa United States
- The Ohio State University United States
Recombination, Genetic, Base Pair Mismatch, Hydrolysis, DNA, DNA Mismatch Repair, Protein Structure, Tertiary, Adenosine Diphosphate, DNA-Binding Proteins, Kinetics, Adenosine Triphosphate, MutS Homolog 2 Protein, Replication Protein A, Humans, Biotinylation, Rad51 Recombinase, Protein Binding
Recombination, Genetic, Base Pair Mismatch, Hydrolysis, DNA, DNA Mismatch Repair, Protein Structure, Tertiary, Adenosine Diphosphate, DNA-Binding Proteins, Kinetics, Adenosine Triphosphate, MutS Homolog 2 Protein, Replication Protein A, Humans, Biotinylation, Rad51 Recombinase, Protein Binding
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