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MMR: MutSalpha binds mismatch in heteroduplex DNA with nick 5' to mismatch
[Homo sapiens]
| GO molecular function: 0030983 |
| Mismatch recognition is performed by the MutS protein. In mammals, there are five homologs (MSH2-6) of MutS, with MSH2, MSH3 and MSH6 having a role in MMR. All mismatches and small indels are recognized by MutSĪ± heterodimer (composed of MSH2 and MSH6), while longer indels are recognized by MutSĪ² (heterodimer of MSH2 and MSH3). First, MutS searches for the mismatch and binds to it in the nucleotide-free or ADP-bound state. The binding of MutS to DNA induces bending of both homo- and heteroduplex DNA. When MutS encounters the mismatch, a bend is turned into a sharp kink. This triggers a conformational change in the protein and the exchange of ADP to ATP. MutS-ATP complex remains stably bound to DNA, but its affinity to the mismatch is reduced. At the same time, the ATP hydrolysis activity of MutS is inhibited. Lastly, the MutS-ATP complex leaves the mismatch and moves along DNA as a sliding clamp to activate downstream repair events near the strand discrimination signal. |
This is the reaction from:
 | Heteroduplex DNA with nick 5' to mismatch in Homo sapiens |
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 | Mismatch in heteroduplex DNA with nick 5' to mismatch bound by MutSalpha in Homo sapiens |
Involved proteins:
References:
| Authors | Title | Journal |
| Antony E, Hingorani MM | Asymmetric ATP binding and hydrolysis activity of the Thermus aquaticus MutS dimer is key to modulation of its interactions with mismatched DNA. |
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| Jacobs-Palmer E, Hingorani MM | The effects of nucleotides on MutS-DNA binding kinetics clarify the role of MutS ATPase activity in mismatch repair. |
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| Lamers MH, Georgijevic D, Lebbink JH, Winterwerp HH, Agianian B, de Wind N, Sixma TK | ATP increases the affinity between MutS ATPase domains. Implications for ATP hydrolysis and conformational changes. |
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| Tessmer I, Yang Y, Zhai J, Du C, Hsieh P, Hingorani MM, Erie DA | Mechanism of MutS searching for DNA mismatches and signaling repair. |
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| Wang H, Yang Y, Schofield MJ, Du C, Fridman Y, Lee SD, Larson ED, Drummond JT, Alani E, Hsieh P, Erie DA | DNA bending and unbending by MutS govern mismatch recognition and specificity. |
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Keywords:
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