ArticleJournal of biomolecular structure & dynamics2012
The molecular origin of the MMR-dependent apoptosis pathway from dynamics analysis of MutSα-DNA complexes.
Article in Journal of biomolecular structure & dynamics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 23 citations in OpenAlex.
- Genomic and Epigenomic Biomarkers of Immune Checkpoint Immunotherapy Response in Melanoma: Current and Future Perspectives.International journal of molecular sciences · 2024Review
- Target-Based Small Molecule Drug Discovery for Colorectal Cancer: A Review of Molecular Pathways and In Silico Studies.Biomolecules · 2022Review
- Bovine Leukemia Virus Infection Affects Host Gene Expression Associated with DNA Mismatch Repair.Pathogens (Basel, Switzerland) · 2020Article
- Loss of mismatch repair signaling impairs the WNT-bone morphogenetic protein crosstalk and the colonic homeostasis.Journal of molecular cell biology · 2020Article
- Mismatch repair protein loss in breast cancer: clinicopathological associations in a large British Columbia cohort.Breast cancer research and treatment · 2020Article
- Existing and Emerging Biomarkers for Immune Checkpoint Immunotherapy in Solid Tumors.Advances in therapy · 2019Review
- Molecular Mechanisms of DNA Replication and Repair Machinery: Insights from Microscopic Simulations.Advanced theory and simulations · 2019Article
- Visualizing correlated motion with HDBSCAN clustering.Protein science : a publication of the Protein Society · 2018Article
- MutSFrontiers in physics · 2017Article
- Uncovering Large-Scale Conformational Change in Molecular Dynamics without Prior Knowledge.Journal of chemical theory and computation · 2016Article
- Long-Range Signaling in MutS and MSH Homologs via Switching of Dynamic Communication Pathways.PLoS computational biology · 2016Article
- Importance of long-time simulations for rare event sampling in zinc finger proteins.Journal of biomolecular structure & dynamics · 2016Article
- Distinct Phenotypes Caused by Mutation of MSH2 in Trypanosome Insect and Mammalian Life Cycle Forms Are Associated with Parasite Adaptation to Oxidative Stress.PLoS neglected tropical diseases · 2015Article
- Recapturing the Correlated Motions of Protein Using Coarse- Grained Models.Protein and peptide letters · 2015Article
- Non-specificity and synergy at the binding site of the carboplatin-induced DNA adduct via molecular dynamics simulations of the MutSα-DNA recognition complex.Journal of biomolecular structure & dynamics · 2014Article
- Destabilization of the MutSα's protein-protein interface due to binding to the DNA adduct induced by anticancer agent carboplatin via molecular dynamics simulations.Journal of molecular modeling · 2013Article
- DNA mismatch repair system: repercussions in cellular homeostasis and relationship with aging.Oxidative medicine and cellular longevity · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The cellular response to DNA damage signaling by mismatch-repair (MMR) proteins is incompletely understood. It is generally accepted that MMR-dependent apoptosis pathway in response to DNA damage detection is independent of MMR's DNA repair function. In this study, we investigate correlated motions in response to the binding of mismatched and platinum cross-linked DNA fragments by MutSα, as derived from 50 ns molecular dynamics simulations. The protein dynamics in response to the mismatched and damaged DNA recognition suggests that MutSα signals their recognition through independent pathways providing evidence for the molecular origin of the MMR-dependent apoptosis. MSH2 subunit is indicated to play a key role in signaling both mismatched and damaged DNA recognition; localized and collective motions within the protein allow identifying sites on the MSH2 surface possible involved in recruiting proteins responsible for downstream events. Unlike in the mismatch complex, predicted key communication sites specific for the damage recognition are on the list of known cancer-causing mutations or deletions. This confirms MSH2's role in signaling DNA damage-induced apoptosis and suggests that defects in MMR alone is sufficient to trigger tumorigenesis, supporting the experimental evidence that MMR-damage response function could protect from the early occurrence of tumors. Identifying these particular communication sites may have implications for the treatment of cancers that are not defective for MMR, but are unable to function optimally for MMR-dependent responses following DNA damage such as the case of resistance to cisplatin.
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.