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Title: Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

The crystal structure of the human MLH1 N-terminus is reported at 2.30 Å resolution. The overall structure is described along with an analysis of two clinically important mutations. 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.
Authors:
; ; ;  [1] ;  [2] ;  [1] ;  [3]
  1. University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada)
  2. Myriad Genetic Laboratories Inc., 320 Wakara Way, Salt Lake City, UT 84108 (United States)
  3. (Canada)
Publication Date:
OSTI Identifier:
22389087
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta crystallographica. Section F, Structural biology communications; Journal Volume: 71; Journal Issue: Pt 8; Other Information: PMCID: PMC4528928; PMID: 26249686; PUBLISHER-ID: hv5298; PUBLISHER-ID: S2053230X15010183; OAI: oai:pubmedcentral.nih.gov:4528928; Copyright (c) Wu et al. 2015; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; BUILDUP; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; CRYSTALS; RESOLUTION; TESTING