ArticleThe Journal of biological chemistry2016
Structural Features and Functional Dependency on β-Clamp Define Distinct Subfamilies of Bacterial Mismatch Repair Endonuclease MutL.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Redundant mispair excision mechanisms in eukaryotic DNA mismatch repair.Nucleus (Austin, Tex.) · 2026Review
- Combining single-molecule and structural studies reveals protein and DNA conformations and assemblies that govern DNA mismatch repair.Current opinion in structural biology · 2024Review
- MutLα suppresses error-prone DNA mismatch repair and preferentially protects noncoding DNA from mutations.The Journal of biological chemistry · 2024Article
- MutLα suppresses error-prone DNA mismatch repair and preferentially protects noncoding DNA from mutations.bioRxiv : the preprint server for biology · 2024Article
- Catalytic mechanism of the zinc-dependent MutL endonuclease reaction.Life science alliance · 2023Article
- Insights into DNA cleavage by MutL homologs from analysis of conserved motifs in eukaryotic Mlh1.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Neural Tube Defects and Folate Deficiency: Is DNA Repair Defective?International journal of molecular sciences · 2023Review
- The methylation-independent mismatch repair machinery inMicrobiology (Reading, England) · 2021Review
- Strand discrimination in DNA mismatch repair.DNA repair · 2021Review
- Spatial coupling between DNA replication and mismatch repair in Caulobacter crescentus.Nucleic acids research · 2021Article
- A Lynch syndrome-associated mutation at a Bergerat ATP-binding fold destabilizes the structure of the DNA mismatch repair endonuclease MutL.The Journal of biological chemistry · 2020Article
- Stochastic Processes and Component Plasticity Governing DNA Mismatch Repair.Journal of molecular biology · 2018Review
- The mutagen and carcinogen cadmium is a high-affinity inhibitor of the zinc-dependent MutLα endonuclease.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In early reactions of DNA mismatch repair, MutS recognizes mismatched bases and activates MutL endonuclease to incise the error-containing strand of the duplex. DNA sliding clamp is responsible for directing the MutL-dependent nicking to the newly synthesized/error-containing strand. In Bacillus subtilis MutL, the β-clamp-interacting motif (β motif) of the C-terminal domain (CTD) is essential for both in vitro direct interaction with β-clamp and in vivo repair activity. A large cluster of negatively charged residues on the B. subtilis MutL CTD prevents nonspecific DNA binding until β clamp interaction neutralizes the negative charge. We found that there are some bacterial phyla whose MutL endonucleases lack the β motif. For example, the region corresponding to the β motif is completely missing in Aquifex aeolicus MutL, and critical amino acid residues in the β motif are not conserved in Thermus thermophilus MutL. We then revealed the 1.35 Å-resolution crystal structure of A. aeolicus MutL CTD, which lacks the β motif but retains the metal-binding site for the endonuclease activity. Importantly, there was no negatively charged cluster on its surface. It was confirmed that CTDs of β motif-lacking MutLs, A. aeolicus MutL and T. thermophilus MutL, efficiently incise DNA even in the absence of β-clamp and that β-clamp shows no detectable enhancing effect on their activity. In contrast, CTD of Streptococcus mutans, a β motif-containing MutL, required β-clamp for the digestion of DNA. We propose that MutL endonucleases are divided into three subfamilies on the basis of their structural features and dependence on β-clamp.
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