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

Journal Article · · Acta Crystallographica. Section F, Structural Biology Communications
 [1];  [1];  [1];  [1];  [2];  [3]
  1. Univ. of Toronto, ON (Canada)
  2. Myriad Genetic Laboratories Inc., Salt Lake City, UT (United States)
  3. Univ. of Toronto, ON (Canada). Dept. of Physiology
+ Show Author Affiliations

Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in theMLH1gene 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. Lastly, the structure shares a high degree of similarity with previously determined prokaryoticMLH1homologs; however, this structure affords a more accurate platform for the classification ofMLH1variants.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC02- 06CH1135
OSTI ID:
1208676
Journal Information:
Acta Crystallographica. Section F, Structural Biology Communications, Vol. 71, Issue 8; ISSN 2053-230X
Publisher:
International Union of CrystallographyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 15 works
Citation information provided by
Web of Science

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Cited By (3)

Functional analysis of rare variants in mismatch repair proteins augments results from computation-based predictive methods journal May 2017
Computational and cellular studies reveal structural destabilization and degradation of MLH1 variants in Lynch syndrome posted_content October 2019
Computational and cellular studies reveal structural destabilization and degradation of MLH1 variants in Lynch syndrome journal November 2019

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