Abstract
Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson-Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot's syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants.
Keywords:
ATPase; GHKL; Lynch syndrome; mismatch repair.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing / chemistry*
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Adaptor Proteins, Signal Transducing / genetics
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Amino Acid Motifs
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Cloning, Molecular
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Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
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Crystallization
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Crystallography, X-Ray
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Gene Expression
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Genetic Predisposition to Disease
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Humans
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Models, Molecular
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Molecular Sequence Data
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MutL Protein Homolog 1
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Nuclear Proteins / chemistry*
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Nuclear Proteins / genetics
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Protein Binding
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Protein Multimerization
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Recombinant Fusion Proteins / chemistry*
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Recombinant Fusion Proteins / genetics
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Structural Homology, Protein
Substances
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Adaptor Proteins, Signal Transducing
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MLH1 protein, human
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Nuclear Proteins
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Recombinant Fusion Proteins
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MutL Protein Homolog 1