What question did this study set out to answer?

To elucidate the molecular mechanism by which the MSH2-MSH6 mismatch repair complex and DNA polymerase eta generate mutations at A:T base pairs during somatic hypermutation in antibody genes.

February 14, 2005The Journal of Experimental MedicineOpen Access

MSH2–MSH6 stimulates DNA polymerase η, suggesting a role for A:T mutations in antibody genes

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Authors

TWTeresa Wilson AVAlexandra Vaisman SMStella Martomo

Discussion

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Overview

Biochemical analysis demonstrates physical and functional interaction between MSH2-MSH6 and DNA polymerase eta, indicating a mechanism for A:T mutations during somatic hypermutation.

Key Points

To elucidate the molecular mechanism by which the MSH2-MSH6 mismatch repair complex and DNA polymerase eta generate mutations at A:T base pairs during somatic hypermutation in antibody genes.
Assessed the in vitro binding specificity of the purified MSH2-MSH6 heterodimer to U:G mismatches and intermediate base excision repair DNA structures.
Tested physical protein-protein interactions between MSH2 and DNA polymerase eta in solution and inside endogenous cell extracts.
Measured the catalytic synthesis activity of DNA polymerase eta in the presence of MSH2-MSH6 using in vitro biochemical assays.
MSH2-MSH6 selectively bound to U:G mismatches but did not bind downstream base excision repair intermediates such as abasic sites or deoxyribose phosphate groups.
MSH2 bound directly to DNA polymerase eta in solution and formed stable endogenous complexes with the polymerase in cell extracts.
MSH2-MSH6 stimulated the in vitro catalytic activity of DNA polymerase eta, demonstrating a direct functional interaction that promotes mutagenic synthesis at A:T base pairs.

Cite This Study

Wilson et al. (2005) studied this question.

synapsesocial.com/papers/6a9bd3d0bce4c781fb6bf03f https://doi.org/10.1084/jem.20042066

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February 14, 2005The Journal of Experimental MedicineOpen Access

MSH2–MSH6 stimulates DNA polymerase η, suggesting a role for A:T mutations in antibody genes

View Full Paper

Ask AI

Bookmark

Authors

TWTeresa Wilson AVAlexandra Vaisman SMStella Martomo

Discussion

Member takes

Overview

Biochemical analysis demonstrates physical and functional interaction between MSH2-MSH6 and DNA polymerase eta, indicating a mechanism for A:T mutations during somatic hypermutation.

Key Points

To elucidate the molecular mechanism by which the MSH2-MSH6 mismatch repair complex and DNA polymerase eta generate mutations at A:T base pairs during somatic hypermutation in antibody genes.
Assessed the in vitro binding specificity of the purified MSH2-MSH6 heterodimer to U:G mismatches and intermediate base excision repair DNA structures.
Tested physical protein-protein interactions between MSH2 and DNA polymerase eta in solution and inside endogenous cell extracts.
Measured the catalytic synthesis activity of DNA polymerase eta in the presence of MSH2-MSH6 using in vitro biochemical assays.
MSH2-MSH6 selectively bound to U:G mismatches but did not bind downstream base excision repair intermediates such as abasic sites or deoxyribose phosphate groups.
MSH2 bound directly to DNA polymerase eta in solution and formed stable endogenous complexes with the polymerase in cell extracts.
MSH2-MSH6 stimulated the in vitro catalytic activity of DNA polymerase eta, demonstrating a direct functional interaction that promotes mutagenic synthesis at A:T base pairs.

Cite This Study

Wilson et al. (2005) studied this question.

synapsesocial.com/papers/6a9bd3d0bce4c781fb6bf03f https://doi.org/10.1084/jem.20042066

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