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Updated: Apr 18, 2026
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
DNA mismatch repair enzymes: genetic defects and autoimmunity
Yoshinao Muro1, Kazumitsu Sugiura1, Tsuneyo Mimori2
1Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Abstract:
DNA mismatch repair (MMR) is one of the several DNA repair pathways conserved from bacteria to humans. The primary function of MMR is to eliminate the mismatch of base-base insertions and deletions that appear as a consequence of DNA polymerase errors at DNA synthesis. The genes encoding the DNA MMR enzymes (MMREs) are highly conserved throughout evolution. In humans, there are two sets of MMREs, corresponding to homologues of the bacterial MutLS systems. The human MutS enzymes consist of MSH2, MSH3 and MSH6, and the human MutL enzymes include MLH1, MLH3, PMS1 and PMS2. Since the beginning of this century, a few reports on autoantibodies to some MMREs have been reported in autoimmune inflammatory myopathy, cancer and hematological disorders. This review charts the functional structures of MMREs, their genetic defects and associated disorders, and autoimmunity to MMREs, including our recent data that was the first to analyze autoantibodies against all seven kinds of MMREs in systemic autoimmune diseases, including idiopathic inflammatory myopathies.
Insights
DNA mismatch repair (MMR) enzymes fix DNA replication errors. Autoantibodies against these DNA repair enzymes are linked to systemic autoimmune diseases, including idiopathic inflammatory myopathies.
Area of Science:
- Molecular Biology
- Genetics
- Immunology
Background:
- DNA mismatch repair (MMR) is a crucial pathway for correcting DNA replication errors like base-base mismatches and insertions/deletions.
- MMR enzymes (MMREs) are highly conserved, with human homologues of bacterial MutLS systems including MSH2, MSH3, MSH6 (MutS) and MLH1, MLH3, PMS1, PMS2 (MutL).
Purpose of the Study:
- To review the functional structures, genetic defects, and associated disorders of DNA mismatch repair enzymes (MMREs).
- To explore the emerging field of autoimmunity targeting MMREs, particularly in systemic autoimmune diseases.
Main Methods:
- Literature review of functional structures, genetic defects, and disorders associated with MMREs.
- Analysis of recent data on autoantibodies against all seven human MMREs in patients with systemic autoimmune diseases.
Main Results:
- MMREs play a vital role in maintaining genomic stability.
- Autoantibodies against MMREs have been reported in various conditions, including autoimmune inflammatory myopathy, cancer, and hematological disorders.
- This study presents novel data on autoantibodies against all seven MMREs in systemic autoimmune diseases.
Conclusions:
- Understanding MMREs' structure and function is key to comprehending associated genetic disorders.
- Autoimmunity against MMREs represents a significant, yet under-explored, aspect of systemic autoimmune diseases.
- Further research into MMRE autoantibodies may reveal new diagnostic or therapeutic targets.
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