DNA mismatch repair protein

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spinqualitylabelsall models E. coli MutS complex with DNA and ATP (PDB id 7ai5) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Disease 3 Structural highlights 4 3D structures of DNA mismatch repair protein Function DNA mismatch repair proteins are key players in genomic stability by signalling mismatches occurring during DNA replication and recombination[1] . MutS is prokaryotic and recognizes base-base mismatches and small insertion/deletion mispairs[2] . MutL enhances recognition of mismatches[3] MutH is the eukaryotic homolog of MutS MLH1, MLH3, PMS1, PMS2 are the human homologs of MutL[4] Disease Mutations in DNA mismatch repair proteins cause hereditary colorectal cancer and loss of these proteins cause significant fraction of sporadic cancers[5]. Structural highlights 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 (residues 1-115) and the (residues 444-503)[6]. In the 3D structure of the mismatch-bound MutS, the DNA strand is kinked by 60 degrees. 3D structures of DNA mismatch repair protein DNA mismatch repair protein 3D structures

References

1. ↑ 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
2. ↑ 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
3. ↑ 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
4. ↑ 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
5. ↑ 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
6. ↑ 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