ArticleNAR cancer2025
Disruption of protein-protein interaction hotspots in the C-terminal domain of MLH1 confers mismatch repair deficiency.
Article in NAR cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed.
- Human PMS1-dependent non-canonical mismatch repair engages with MBD4 to repair methylated CpG deamination.Nucleic acids research · 2026Article
- Targeted quantification assays for DNA repair and handling proteins and interactions in Huntington's disease models.bioRxiv : the preprint server for biology · 2026Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
MutLα, a heterodimer of MLH1 and PMS2, plays a key role in DNA mismatch repair (MMR), which maintains genomic stability by correcting replication errors. Loss of MLH1 function causes MMR deficiency (MMRd), leading to elevated mutation rates and increased cancer susceptibility. However, MMRd can offer a therapeutic advantage, as high tumour mutational burden enhances the efficacy of immune checkpoint inhibition. MMR also drives somatic expansion of CAG repeats linked to Huntington's disease (HD) pathogenesis. The C-terminal domain (CTD) of MLH1 contains at least two distinct protein-protein interaction (PPI) sites. The S1 site supports heterodimerization with the PMS2 endonuclease, whereas the S2 site interacts with MIP-boxes present in MMR-associated factors (EXO1, MSH3) and in the DNA repair nuclease FAN1. Here, using MLH1-S2 mutant cell models and synthetic FAN1-derived peptides containing two adjacent MLH1-binding motifs (MIP and MIM), we demonstrate that selective disruption of MLH1 PPIs impairs MMR
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.