DNA mismatch repair protein
From Proteopedia
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| - | <StructureSection load='7ai5' size='340' side='right' caption='E. coli MutS complex with DNA and ATP (PDB id [[7ai5]])' scene=''> | + | <StructureSection load='7ai5' size='340' side='right' caption='E. coli MutS complex with DNA and ATP (PDB id [[7ai5]])' scene='91/916389/Cv/1'> |
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'''DNA mismatch repair proteins''' are key players in genomic stability by signalling mismatches occurring during DNA replication and recombination<ref>PMID:18157157</ref> .<br/> | '''DNA mismatch repair proteins''' are key players in genomic stability by signalling mismatches occurring during DNA replication and recombination<ref>PMID:18157157</ref> .<br/> | ||
| - | '''MutS''' is prokaryotic and recognizes base-base mismatches and small insertion/deletion mispairs<ref>PMID:11048711</ref> .<br /> | + | *'''MutS''' is prokaryotic and recognizes base-base mismatches and small insertion/deletion mispairs<ref>PMID:11048711</ref> .<br /> |
| - | '''MutL''' enhances recognition of mismatches<ref>PMID:15470502</ref> <br /> | + | *'''MutL''' enhances recognition of mismatches<ref>PMID:15470502</ref> <br /> |
| - | '''MutH''' is the eukaryotic homolog of MutS <br /> | + | *'''MutH''' is the eukaryotic homolog of MutS. See also [[DNA Repair]] <br /> |
| - | '''MLH1, MLH3, PMS1, PMS2''' are the human homologs of MutL<ref>PMID:15475387</ref> <br /> | + | *'''MLH1, MLH3, PMS1, PMS2''' are the human homologs of MutL<ref>PMID:15475387</ref> <br /> |
== Disease == | == Disease == | ||
Mutations in DNA mismatch repair proteins cause hereditary colorectal cancer and loss of these proteins cause significant fraction of sporadic cancers<ref>PMID:18406444</ref>. | Mutations in DNA mismatch repair proteins cause hereditary colorectal cancer and loss of these proteins cause significant fraction of sporadic cancers<ref>PMID:18406444</ref>. | ||
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| - | == Relevance == | ||
== Structural highlights == | == Structural highlights == | ||
| - | The complex between E. coli MutS and DNA shows the DNA clamped between the two MutS monomers and held by the mismatch binding domain (residues 1-115) and the clamp domain (residues 444-503 <ref>PMID:33820992</ref> | + | MutS is composed of several domains: N-terminal mismatch-recognition domain; connector domain; core domain; clamp domain; ATPase domain; helix-turn-helix domain. The complex between ''E. coli'' MutS and DNA in the scanning mode shows the straight DNA strand clamped between the two MutS monomers and held by the <scene name='91/916389/Cv/2'>mismatch binding domain</scene> (residues 1-115) and the <scene name='91/916389/Cv/3'>clamp domain</scene> (residues 444-503)<ref>PMID:33820992</ref>. In the 3D structure of the mismatch-bound MutS, the DNA strand is kinked by 60 degrees. |
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| + | ==3D structures of DNA mismatch repair protein== | ||
| + | [[DNA mismatch repair protein 3D structures]] | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
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References
- ↑ Li GM. Mechanisms and functions of DNA mismatch repair. Cell Res. 2008 Jan;18(1):85-98. doi: 10.1038/cr.2007.115. PMID:18157157 doi:http://dx.doi.org/10.1038/cr.2007.115
- ↑ Lamers MH, Perrakis A, Enzlin JH, Winterwerp HH, de Wind N, Sixma TK. The crystal structure of DNA mismatch repair protein MutS binding to a G x T mismatch. Nature. 2000 Oct 12;407(6805):711-7. PMID:11048711 doi:10.1038/35037523
- ↑ Guarne A, Ramon-Maiques S, Wolff EM, Ghirlando R, Hu X, Miller JH, Yang W. Structure of the MutL C-terminal domain: a model of intact MutL and its roles in mismatch repair. EMBO J. 2004 Oct 27;23(21):4134-45. Epub 2004 Oct 7. PMID:15470502
- ↑ Ellison AR, Lofing J, Bitter GA. Human MutL homolog (MLH1) function in DNA mismatch repair: a prospective screen for missense mutations in the ATPase domain. Nucleic Acids Res. 2004 Oct 8;32(18):5321-38. doi: 10.1093/nar/gkh855. Print, 2004. PMID:15475387 doi:http://dx.doi.org/10.1093/nar/gkh855
- ↑ Hsieh P, Yamane K. DNA mismatch repair: molecular mechanism, cancer, and ageing. Mech Ageing Dev. 2008 Jul-Aug;129(7-8):391-407. doi: 10.1016/j.mad.2008.02.012., Epub 2008 Mar 4. PMID:18406444 doi:http://dx.doi.org/10.1016/j.mad.2008.02.012
- ↑ Fernandez-Leiro R, Bhairosing-Kok D, Kunetsky V, Laffeber C, Winterwerp HH, Groothuizen F, Fish A, Lebbink JHG, Friedhoff P, Sixma TK, Lamers MH. The selection process of licensing a DNA mismatch for repair. Nat Struct Mol Biol. 2021 Apr;28(4):373-381. doi: 10.1038/s41594-021-00577-7., Epub 2021 Apr 5. PMID:33820992 doi:http://dx.doi.org/10.1038/s41594-021-00577-7
