Conformational trapping of mismatch recognition complex MSH2/MSH3 on repair-resistant DNA loops
| Autor: | Cynthia T. McMurray, Julie E. Coats, Walter H. Lang, Yuyen Lin, Greg L. Hura, Jerzy Majka, Ivan Rasnik |
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| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular congenital hereditary and neonatal diseases and abnormalities Base Pair Mismatch Protein Conformation Biology In Vitro Techniques DNA Mismatch Repair chemistry.chemical_compound Protein structure Fluorescence Resonance Energy Transfer Humans MutS Homolog 2 Protein Multidisciplinary Binding Sites Base Sequence DNA Molecular biology Recombinant Proteins DNA-Binding Proteins chemistry MSH3 Amino Acid Substitution PNAS Plus MSH2 Multiprotein Complexes MutS Homolog 3 Protein Biophysics Mutagenesis Site-Directed Nucleic Acid Conformation DNA mismatch repair Heteroduplex Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 108(42) |
| ISSN: | 1091-6490 |
| Popis: | Insertion and deletion of small heteroduplex loops are common mutations in DNA, but why some loops are prone to mutation and others are efficiently repaired is unknown. Here we report that the mismatch recognition complex, MSH2/MSH3, discriminates between a repair-competent and a repair-resistant loop by sensing the conformational dynamics of their junctions. MSH2/MSH3 binds, bends, and dissociates from repair-competent loops to signal downstream repair. Repair-resistant Cytosine-Adenine-Guanine (CAG) loops adopt a unique DNA junction that traps nucleotide-bound MSH2/MSH3, and inhibits its dissociation from the DNA. We envision that junction dynamics is an active participant and a conformational regulator of repair signaling, and governs whether a loop is removed by MSH2/MSH3 or escapes to become a precursor for mutation. |
| Databáze: | OpenAIRE |
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