Familial Cancer

, Volume 12, Issue 2, pp 159–168

The mechanism of mismatch repair and the functional analysis of mismatch repair defects in Lynch syndrome

Original Article

DOI: 10.1007/s10689-013-9635-x

Cite this article as:
Martín-López, J.V. & Fishel, R. Familial Cancer (2013) 12: 159. doi:10.1007/s10689-013-9635-x


The majority of Lynch syndrome (LS), also known as hereditary non-polyposis colorectal cancer (HNPCC), has been linked to heterozygous defects in DNA mismatch repair (MMR). MMR is a highly conserved pathway that recognizes and repairs polymerase misincorporation errors and nucleotide damage as well as functioning as a damage sensor that signals apoptosis. Loss-of-heterozygosity (LOH) that retains the mutant MMR allele and epigenetic silencing of MMR genes are associated with an increased mutation rate that drives carcinogenesis as well as microsatellite instability that is a hallmark of LS/HNPCC. Understanding the biophysical functions of the MMR components is crucial to elucidating the role of MMR in human tumorigenesis and determining the pathogenetic consequences of patients that present in the clinic with an uncharacterized variant of the MMR genes. We summarize the historical association between LS/HNPCC and MMR, discuss the mechanism of the MMR and finally examine the functional analysis of MMR defects found in LS/HNPCC patients and their relationship with the severity of the disease.


DNA mismatch repair system Lynch syndrome Hereditary non polyposis colorectal cancer (HNPCC) Functional defects hMSH2–hMSH6 hMLH1–hPMS2 

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer GeneticsThe Ohio State University Wexner Medical CenterColumbusUSA
  2. 2.Physics DepartmentThe Ohio State UniversityColumbusUSA

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