Affinage

MUTYH

Adenine DNA glycosylase · UniProt Q9UIF7

Length
546 aa
Mass
60.1 kDa
Annotated
2026-06-10
100 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MUTYH is a base-excision repair adenine-DNA glycosylase that removes adenine misincorporated opposite 8-oxoguanine (A:8-oxoG), suppressing the G:C→T:A transversions that arise from oxidative DNA damage (PMID:18534194, PMID:34142156). It functions in both nuclear and mitochondrial genomes, with compartment targeting governed by alternative splicing and an intact C-terminal region required for nuclear localization (PMID:11554314, PMID:15180946). Structural and biochemical work resolved how MUTYH recognizes and excises the A:8-oxoG mispair and how its C-terminal domain engages PCNA for replication-coupled repair, consistent with its detection on nascent DNA at replication forks (PMID:34142156, PMID:28575236). After adenine excision, MUTYH coordinates downstream steps: its C-terminal domain transiently protects the abasic product from premature APE1 incision and OGG1 action (PMID:15199168), while UV-DDB relieves this product inhibition to accelerate MUTYH turnover from abasic sites (PMID:34232996), and DNA polymerase λ, FEN1, and DNA ligase I complete repair (PMID:19820168). The interdomain connector, which carries a Zn-binding His/Cys motif, is a scaffold for partners that enhance repair efficiency, including the 9-1-1 checkpoint clamp (Hus1/Rad1), APE1, and SIRT6, which assemble at oxidative damage sites without mutual competition (PMID:16879101, PMID:24209961, PMID:26063178); MUTYH also organizes WRN and Pol λ focus formation at 8-oxoG:A lesions (PMID:22753033). A redox-active [4Fe4S] cluster is essential for DNA-mediated localization to lesions, and its loss in pathogenic variants abolishes redox signalling and impairs activity (PMID:29915346). Beyond repair, MUTYH-generated single-strand breaks initiate p53- and PARP-dependent and calpain-dependent caspase-independent cell death pathways that suppress tumorigenesis but drive neurodegeneration, microglial activation, and photoreceptor loss under chronic oxidative stress (PMID:21235684, PMID:23143307, PMID:25310643, PMID:27699246). Numerous MUTYH missense and truncating variants abolish glycosylase and DNA-binding activity, linking loss of this repair function to colorectal tumorigenesis (PMID:18534194, PMID:25820570).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2001 Medium

    Established that MUTYH initiates oxidative base-excision repair in both nuclear and mitochondrial genomes, defining the compartmental scope of its action via alternative splicing.

    Evidence Subcellular fractionation, immunodetection, and splicing analysis in human cells

    PMID:11554314

    Open questions at the time
    • Splice isoform sequences not fully mapped
    • Relative repair contribution of each compartment not quantified
  2. 2004 High

    Showed that the MUTYH C-terminal domain protects the abasic product from premature APE1/OGG1 action, revealing intrinsic coordination of repair handoff; nuclear localization was mapped to the intact C-terminal region.

    Evidence In vitro glycosylase/cell-free extract assays with mutagenesis; RT-PCR and immunofluorescence of a splice variant

    PMID:15180946 PMID:15199168

    Open questions at the time
    • Structural basis of product protection not resolved here
    • Nuclear import signal not precisely defined
  3. 2006 High

    Identified the 9-1-1 checkpoint clamp (Hus1/Rad1) as a direct MUTYH partner that stimulates glycosylase activity, connecting base repair to DNA damage checkpoint signalling.

    Evidence Reciprocal Co-IP across species, yeast two-hybrid mapping, glycosylase assay, mutagenesis, co-localization

    PMID:16879101

    Open questions at the time
    • Stoichiometry of the MUTYH–9-1-1 complex unknown
    • In vivo checkpoint consequence of this interaction not quantified
  4. 2008 High

    Systematically classified disease-associated MUTYH variants by their glycosylase and DNA-binding defects, providing a functional basis for genotype interpretation.

    Evidence In vitro glycosylase and DNA binding assays on purified recombinant variants

    PMID:18534194

    Open questions at the time
    • In vitro defects not all linked to clinical outcomes
    • Effects on protein stability vs catalysis not separated for all variants
  5. 2009 High

    Reconstituted the complete A:8-oxoG repair pathway and showed MUTYH recruits pol λ, PCNA, FEN1, and DNA ligase, while genetic epistasis distinguished MUTYH from MSH2-dependent oxidative repair.

    Evidence In vitro BER reconstitution with purified proteins, recruitment immunofluorescence, and Msh2/Mutyh double-knockout mouse analysis

    PMID:19435918 PMID:19820168

    Open questions at the time
    • Order and timing of factor handoffs not fully resolved
    • Tissue-specificity of MSH2/MUTYH overlap unexplained
  6. 2011 Medium

    Demonstrated that MUTYH-generated single-strand breaks initiate two distinct caspase-independent cell death pathways (nuclear PARP-dependent, mitochondrial calpain-dependent), reframing MUTYH as both a repair enzyme and a death-signalling trigger.

    Evidence Knockout mouse models with PARP and calpain inhibitor pharmacology and SSB measurement

    PMID:21235684

    Open questions at the time
    • Molecular link from SSB to each death effector incomplete
    • Single lab
  7. 2012 High

    Extended the death-pathway model to neurodegeneration and identified WRN/Pol λ as MUTYH-dependent downstream repair factors at 8-oxoG:A lesions.

    Evidence Multiple genetic KO mouse combinations with pathway dissection; Co-IP, focus-formation, siRNA, and in vitro Pol λ stimulation assays

    PMID:22753033 PMID:23143307

    Open questions at the time
    • Triggers of compartment-specific death not fully defined
    • Human neuronal relevance not directly tested
  8. 2013 High

    Mapped the APE1 interaction to the MUTYH interdomain connector at residue level and showed Hus1 stabilizes the complex, defining the IDC as a multi-partner repair scaffold; cellular assays confirmed a protective role against oxidative stress.

    Evidence NMR chemical shift perturbation, Co-IP, in vitro binding; siRNA/overexpression with viability and 8-oxoG readouts

    PMID:24209961 PMID:24315136

    Open questions at the time
    • Dynamics of partner exchange on the IDC unresolved
    • Cellular phenotype work is single lab
  9. 2014 Medium

    Placed MUTYH transcriptionally downstream of p53 and mechanistically within a p53/PARP-dependent caspase-independent death pathway, linking repair capacity to tumor-suppressive cell death.

    Evidence p53-binding-site luciferase reporter, siRNA, and pharmacological inhibitor epistasis in colorectal cancer cells

    PMID:25310643

    Open questions at the time
    • Direct p53 occupancy in vivo not shown
    • Single lab
  10. 2015 High

    Defined SIRT6 as an additional IDC partner that, with APE1 and Hus1, cooperatively enhances complex assembly and chromatin recruitment; an E. coli complementation screen functionally classified 47 variants.

    Evidence Co-IP, IDC mutagenesis, laser-damage co-localization, chromatin fractionation; in vivo MutY-complementation assay with structural modeling

    PMID:25820570 PMID:26063178

    Open questions at the time
    • Functional role of telomeric MYH relocalization upon SIRT6 loss unknown
    • Complementation lacks human-protein biochemical reconstitution
  11. 2017 Medium

    Established that MUTYH operates post-replicatively at the replication fork by detecting it on nascent DNA.

    Evidence iPOND coupled with targeted mass spectrometry on nascent DNA

    PMID:28575236

    Open questions at the time
    • Direct coupling to fork-associated machinery not shown
    • Single lab
  12. 2018 High

    Demonstrated that the redox-active [4Fe4S] cluster is essential for MUTYH's DNA-mediated lesion localization, and that a pathogenic variant disrupts cluster integrity.

    Evidence DNA electrochemistry, EPR, DNA binding and glycosylase assays with mutagenesis

    PMID:29915346

    Open questions at the time
    • In vivo contribution of redox search to repair kinetics not quantified
    • Generality across other variants untested
  13. 2021 High

    Resolved the structural basis of A:8-oxoG recognition and PCNA-coupled repair and defined the IDC Zn-binding motif; identified UV-DDB as a turnover factor that relieves MUTYH product inhibition at abasic sites.

    Evidence X-ray crystallography of MUTYH–DNA and MUTYH C-terminal–PCNA complexes; bulk kinetics, EMSA, AFM, and single-molecule imaging of UV-DDB displacement

    PMID:34142156 PMID:34232996

    Open questions at the time
    • Coordination of UV-DDB with APE1/PCNA handoff not integrated
    • Human full-length structure with partners not solved
  14. 2016 Medium

    Showed disease contexts where MUTYH activity is deleterious: microglial BER drives photoreceptor death in retinitis pigmentosa, and MUTYH/OGG1 incisions on 8-oxoG-containing repeats create conditions for trinucleotide-repeat expansion.

    Evidence Mutyh KO in rd10 mouse with SSB/PARP readouts; in vitro BER on TNR substrates with HD mouse brain correlation

    PMID:26980281 PMID:27699246

    Open questions at the time
    • Causality of MUTYH in human repeat-expansion disease not shown
    • Full repeat-expansion mechanism not reconstituted

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the competing repair-completing and death-signalling fates of a MUTYH-generated abasic site/SSB are selected in vivo, and how partner exchange on the IDC is temporally regulated, remain unresolved.
  • No mechanism distinguishing productive repair from death-triggering breaks
  • Temporal ordering of IDC partner binding unknown
  • Mitochondrial MUTYH repair pathway less characterized than nuclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0140097 catalytic activity, acting on DNA 3 GO:0003677 DNA binding 2 GO:0016787 hydrolase activity 2
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2 GO:0005739 mitochondrion 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-73894 DNA Repair 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
APE1DDB2HUS1PCNAPOLLRAD1SIRT6WRN
Complex memberships
9-1-1 (Hus1/Rad1) checkpoint clamp

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Human MYH (hMYH) protein is localized to both nucleus and mitochondria, regulated by alternative splicing of its transcript, establishing that MUTYH initiates base excision repair of oxidized bases in both genomic compartments. Subcellular fractionation, immunodetection, alternative splicing analysis in human cells Progress in nucleic acid research and molecular biology Medium 11554314
2004 MUTYH C-terminal domain prevents APE1 from incising the AP site generated after adenine excision from A:8-oxoG, and prevents OGG1 from excising 8-oxoG opposite the AP site. Mutations R361A and G365D in the C-terminal domain abolished this protective function without affecting glycosylase activity, demonstrating that product protection is an intrinsic function of the C-terminal domain. In vitro glycosylase assay with recombinant proteins, site-directed mutagenesis, cell-free extract assays Nucleic acids research High 15199168
2004 A splice-site variant (IVS10-2A>G) of MYH produces an aberrant mRNA encoding a truncated protein that is NOT localized to the nucleus, demonstrating that nuclear localization of wild-type MYH requires the intact C-terminal region encoded by exon 10 onward. RT-PCR for aberrant transcript detection; immunofluorescence for subcellular localization of wild-type vs. variant protein Carcinogenesis Medium 15180946
2006 Human MYH physically interacts with the checkpoint clamp proteins Hus1 and Rad1 (but not Rad9) of the 9-1-1 complex. The major Hus1-binding site maps to residues 295–350 of hMYH (interdomain connector). Val315 is critical for Hus1 binding. The 9-1-1 complex stimulates SpMYH glycosylase activity, and MYH-Hus1 interaction is enhanced following ionizing radiation; MYH nuclear foci co-localize with Rad9 foci after H2O2 treatment. Co-immunoprecipitation (human and S. pombe), yeast two-hybrid mapping, in vitro glycosylase activity assay, site-directed mutagenesis, immunofluorescence co-localization The Biochemical journal High 16879101
2008 Nine MUTYH missense/frameshift mutants and two SNPs were characterized for DNA glycosylase and DNA binding activities in vitro. Y165C, R231H, and P281L were severely defective in both activities; R260Q and G382D were partially active; frameshift mutants (Y90X, Q377X, E466X, 1103delC) completely lacked both activities. SNP Q324H was partially impaired in adenine removal. In vitro glycosylase assay and DNA binding assay with synthetic oligonucleotide substrates, PAGE analysis of cleavage products Gastroenterology High 18534194
2009 MUTYH and DNA polymerase lambda (pol λ) together reconstitute the complete base excision repair pathway for A:8-oxoG mispairs. MUTYH, pol λ, PCNA, FEN1, and DNA ligases I and III are specifically recruited from human cell extracts to A:8-oxoG DNA. Full-pathway repair was reconstituted in vitro using purified human MUTYH, pol λ, FEN1, and DNA ligase I. In vitro BER reconstitution with purified human proteins; immunofluorescence of protein recruitment in ROS-treated cells Proceedings of the National Academy of Sciences of the United States of America High 19820168
2009 MSH2 and MUTYH provide largely separate, independent repair functions for oxidative DNA damage in vivo. Msh2−/−Mutyh−/− mouse embryo fibroblasts show 8-oxoG levels comparable to single knockouts, but synergistic 8-oxoG accumulation occurs in vivo tissues. Paradoxically, Msh2−/−Mutyh−/− mice show delayed lymphomagenesis relative to Msh2−/− mice, indicating that a large fraction of the cancer phenotype of Msh2 deficiency depends on MUTYH activity. Double knockout mouse model, hprt mutation frequency assay in MEFs, 8-oxoG measurement by immunoassay, tumor incidence analysis Cancer research High 19435918
2011 MUTYH-generated single-strand breaks (SSBs) in nuclear DNA trigger PARP-dependent cell death, while SSBs in mitochondrial DNA trigger calpain-dependent neuronal loss, revealing that MUTYH initiates two distinct caspase-independent death pathways. Loss of MUTYH suppresses programmed cell death under oxidative stress, allowing escape from death but accumulation of mutations in APC/KRAS. Genetic KO mouse models (MUTYH−/−, OGG1/MUTYH double KO), PARP inhibitor and calpain inhibitor pharmacology, measurement of SSBs Cancer science Medium 21235684
2012 MUTYH-mediated excision repair of 8-oxoG-paired adenine triggers neurodegeneration. MUTYH-deficient (Mutyh−/−) or OGG1/MUTYH double-KO mice were resistant to striatal neurodegeneration caused by 8-oxoG accumulation, whereas OGG1−/− or MTH1−/− mice showed severe degeneration. MUTYH-generated SSBs in neuronal mitochondrial DNA activated calpain-dependent death; delayed nuclear 8-oxoG accumulation in microglia triggered PARP-AIF-dependent microgliosis. Genetic KO mouse models (Mutyh−/−, Ogg1−/−, Mth1−/−, double/triple combinations), mtDNA 8-oxoG quantification, PARP/calpain pathway analysis, histopathology The Journal of clinical investigation High 23143307
2013 MYH physically interacts with APE1 via the interdomain connector (IDC). NMR chemical shift perturbation mapped the hMYH IDC peptide binding to the DNA-binding site of APE1 and a distal site (key residues N212 and Q137 of APE1). Hus1 stabilizes the MYH/APE1 complex both in vitro and in cells without competing for MYH binding. NMR chemical shift perturbation, Co-IP in cells, in vitro binding assays DNA repair High 24209961
2013 MYH knockdown in HeLa cells increases sensitivity to H2O2, elevates 8-oxoG levels, alters cell cycle progression, and enhances apoptosis after oxidative stress. Overexpression of mouse Myh in MMR-defective HCT15 cells confers resistance to oxidant killing and apoptosis, establishing a protective role in the cellular response to oxidative DNA damage. siRNA knockdown and cDNA overexpression, cell viability assays, flow cytometry, immunofluorescence for 8-oxoG DNA repair Medium 24315136
2014 MUTYH is transcriptionally regulated by p53 through a functional p53-binding site in the MUTYH gene, identified in MLH1-proficient colorectal cancer cells. MUTYH mediates p53-dependent, PARP-dependent caspase-independent cell death; siRNA knockdown of MUTYH, p53 inhibition, or PARP inhibition each suppressed cell death without additive effect, placing MUTYH downstream of p53 in this pathway. Luciferase reporter assay for p53 binding site, siRNA knockdown, pharmacological inhibitors (p53 inhibitor, PARP inhibitor), cell death assays Oncogenesis Medium 25310643
2015 SIRT6 physically interacts with MYH glycosylase, APE1, and the 9-1-1 checkpoint clamp. These interactions are enhanced after oxidative stress. SIRT6, APE1, and Hus1 all bind the interdomain connector (IDC) of MYH at overlapping but distinct motifs and do not compete; instead, each partner enhances the others' association with MYH. MYH and SIRT6 are co-recruited to oxidative DNA damage sites in transcriptionally active chromatin; Sirt6 depletion causes MYH foci to localize on telomeres. Co-IP, site-directed mutagenesis of IDC, immunofluorescence at laser-induced damage sites, chromatin fractionation BMC molecular biology High 26063178
2015 Functional complementation assay in MutY-disrupted E. coli for 47 MUTYH missense variants established which variants severely impair MUTYH glycosylase function (fail to suppress G:C→T:A mutations) vs. retain near-wild-type activity. Structural prediction based on MutY crystal structure allowed interpretation of effects on catalytic activity or protein stability. In vivo complementation assay (spontaneous mutation rate in MutY-deficient E. coli), site-directed mutagenesis, in silico structural modeling Human mutation Medium 25820570
2017 BER/SSBR proteins including MYH are present on nascent DNA at replication forks, demonstrated by iPOND (isolation of proteins on nascent DNA) coupled with targeted mass spectrometry, establishing that MYH operates post-replicatively at the replication fork. iPOND combined with targeted mass spectrometry on nascent DNA in human cells Nucleic acids research Medium 28575236
2018 Wild-type human MUTYH contains a redox-active [4Fe4S] cluster. The pathogenic variant MUTYH C306W (cysteine ligating the cluster replaced by tryptophan) undergoes rapid oxidative degradation of its [4Fe4S]2+ cluster to [3Fe4S]+, abolishing redox signalling, reducing DNA binding, and impairing enzymatic function. This demonstrates that redox activity of the [4Fe4S] cluster is essential for MUTYH's DNA damage localization mechanism. DNA electrochemistry, EPR spectroscopy, DNA binding assay, glycosylase activity assay, site-directed mutagenesis Nature chemistry High 29915346
2021 Crystal structures of mouse MUTYH in complex with DNA and of the MUTYH C-terminal domain with human PCNA revealed the molecular mechanism for A:8-oxoG mispair recognition and excision, including the role of PCNA in replication-coupled repair. The Zn-binding motif in the IDC was resolved as one histidine and three cysteine residues. The IDC surface exposure explains interaction modes with 9-1-1 and APE1. Several MAP mutations perturb residues critical to catalytic function. X-ray crystallography (MUTYH–DNA complex; MUTYH C-terminal domain–PCNA complex), structural analysis Nucleic acids research High 34142156
2021 UV-DDB stimulates MUTYH turnover 4–5-fold by directly interacting with MUTYH and displacing it from abasic sites (product inhibition relief). Single-molecule fluorescence showed UV-DDB decreases MUTYH half-life on abasic-site DNA from ~8800 s to ~590 s. EMSA and AFM confirmed transient complex formation between MUTYH and UV-DDB. Bulk kinetic assay, EMSA, atomic force microscopy, single-molecule fluorescence imaging Nucleic acids research High 34232996
2016 MUTYH-mediated base excision repair in microglia promotes microglial activation and photoreceptor cell death in a mouse model of retinitis pigmentosa (rd10 mice). Mutyh deficiency prevented SSB formation in microglia, suppressed microglial activation and the inflammatory/cytotoxic phenotype under oxidative stress, and reduced photoreceptor cell death. Mutyh knockout in rd10 mouse model, immunofluorescence for SSBs and PARP activation, primary microglial culture under oxidative stress, histopathology JCI insight Medium 27699246
2012 Werner syndrome helicase (WRN) is recruited to 8-oxoG:A mispairs in a manner dependent on DNA polymerase λ (Polλ). MUTYH is required for nuclear focus formation of both WRN and Polλ following oxidative stress. WRN binds the catalytic domain of Polλ and specifically stimulates gap-filling by Polλ over 8-oxoG. MUTYH depletion suppresses hypersensitivity of WRN/Polλ-deficient cells to oxidative stress. Co-immunoprecipitation, immunofluorescence (focus formation), siRNA knockdown, cell viability assay, in vitro DNA synthesis assay with purified proteins Nucleic acids research High 22753033
2016 MUTYH glycosylase activity on 8-oxoG-containing trinucleotide repeat sequences generates closely spaced incisions on opposite strands (together with OGG1), creating conditions permissive for CAG/CTG repeat expansion in vitro. This was confirmed in R6/2 HD mouse brain areas showing elevated 8-oxodG and expression of both glycosylases. In vitro BER assay on TNR substrates with purified OGG1, MUTYH, and pol β; immunohistochemistry and 8-oxodG measurement in HD mouse brain Nucleic acids research Medium 26980281

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. The New England journal of medicine 603 12606733
2002 Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-->T:A mutations. Human molecular genetics 299 12393807
2004 Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk. Journal of the National Cancer Institute 190 15523092
2012 Prevalence and phenotypes of APC and MUTYH mutations in patients with multiple colorectal adenomas. JAMA 174 22851115
2004 MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps. Gastroenterology 156 15236166
2004 Accumulation of the oxidative base lesion 8-hydroxyguanine in DNA of tumor-prone mice defective in both the Myh and Ogg1 DNA glycosylases. Cancer research 136 15231648
2008 Hyperplastic polyps and sessile serrated adenomas as a phenotypic expression of MYH-associated polyposis. Gastroenterology 133 19013464
2001 Regulation of intracellular localization of human MTH1, OGG1, and MYH proteins for repair of oxidative DNA damage. Progress in nucleic acid research and molecular biology 133 11554314
2008 Analysis of MUTYH genotypes and colorectal phenotypes in patients With MUTYH-associated polyposis. Gastroenterology 131 19032956
2006 Hyperplastic polyposis syndrome: phenotypic presentations and the role of MBD4 and MYH. Gastroenterology 131 16831587
2010 MUTYH-associated polyposis (MAP). Critical reviews in oncology/hematology 126 20663686
2012 8-Oxoguanine causes neurodegeneration during MUTYH-mediated DNA base excision repair. The Journal of clinical investigation 114 23143307
2009 An 8-oxo-guanine repair pathway coordinated by MUTYH glycosylase and DNA polymerase lambda. Proceedings of the National Academy of Sciences of the United States of America 103 19820168
2010 A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants. British journal of cancer 96 21063410
2017 Repair of 8-oxoG:A mismatches by the MUTYH glycosylase: Mechanism, metals and medicine. Free radical biology & medicine 85 28087410
2008 Characterization of mutant MUTYH proteins associated with familial colorectal cancer. Gastroenterology 85 18534194
2008 Association of MUTYH Gln324His and APEX1 Asp148Glu with colorectal cancer and smoking in a Japanese population. Journal of experimental & clinical cancer research : CR 84 18823566
2014 Biallelic MUTYH mutations can mimic Lynch syndrome. European journal of human genetics : EJHG 83 24518836
2006 Physical and functional interactions between MutY glycosylase homologue (MYH) and checkpoint proteins Rad9-Rad1-Hus1. The Biochemical journal 82 16879101
2013 Role of MUTYH in human cancer. Mutation research 80 23507534
2005 MutYH (MYH) and colorectal cancer. Biochemical Society transactions 80 16042573
2004 High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis. Gastroenterology 74 15188161
2011 DNA glycosylase encoded by MUTYH functions as a molecular switch for programmed cell death under oxidative stress to suppress tumorigenesis. Cancer science 73 21235684
2010 MSH6 and MUTYH deficiency is a frequent event in early-onset colorectal cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 73 20924129
2004 Germline MUTYH (MYH) mutations in Portuguese individuals with multiple colorectal adenomas. Human mutation 72 15366000
2013 MUTYH DNA glycosylase: the rationale for removing undamaged bases from the DNA. Frontiers in genetics 67 23450852
2008 MUTYH Associated Polyposis (MAP). Current genomics 66 19506731
2006 Association of MUTYH and colorectal cancer. British journal of cancer 66 16804517
2011 MutYH mutation carriers have increased breast cancer risk. Cancer 65 21952991
2005 Attenuated familial adenomatous polyposis and Muir-Torre syndrome linked to compound biallelic constitutional MYH gene mutations. Clinical genetics 64 16207212
2017 NTHL1 and MUTYH polyposis syndromes: two sides of the same coin? The Journal of pathology 63 29105096
2004 Role of inherited defects of MYH in the development of sporadic colorectal cancer. Genes, chromosomes & cancer 62 15034862
2020 MUTYH: Not just polyposis. World journal of clinical oncology 58 32821650
2017 A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors. Endocrine-related cancer 57 28634180
2010 MYH-9 Related Platelet Disorders: Strategies for Management and Diagnosis. Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie 57 21113248
2011 Association between monoallelic MUTYH mutation and colorectal cancer risk: a meta-regression analysis. Familial cancer 55 21061173
2014 Six homeoproteins and a Iinc-RNA at the fast MYH locus lock fast myofiber terminal phenotype. PLoS genetics 54 24852826
2009 MUTYH Gln324His gene polymorphism and genetic susceptibility for lung cancer in a Japanese population. Journal of experimental & clinical cancer research : CR 54 19161591
2004 A novel splice-site variant of the base excision repair gene MYH is associated with production of an aberrant mRNA transcript encoding a truncated MYH protein not localized in the nucleus. Carcinogenesis 54 15180946
2014 Prevalence and characteristics of MUTYH-associated polyposis in patients with multiple adenomatous and serrated polyps. Clinical cancer research : an official journal of the American Association for Cancer Research 50 24470512
2022 Inherited MUTYH mutations cause elevated somatic mutation rates and distinctive mutational signatures in normal human cells. Nature communications 49 35803914
2009 Role of MUTYH and MSH2 in the control of oxidative DNA damage, genetic instability, and tumorigenesis. Cancer research 48 19435918
2006 Prevalence of MYH germline mutations in Swiss APC mutation-negative polyposis patients. International journal of cancer 48 16287072
2006 Germline mutations and polymorphic variants in MMR, E-cadherin and MYH genes associated with familial gastric cancer in Jiangsu of China. International journal of cancer 47 16929514
2004 The multiple colorectal adenoma phenotype and MYH, a base excision repair gene. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 47 15290654
2009 MUTYH-associated polyposis. Best practice & research. Clinical gastroenterology 44 19414147
2006 The role of MYH and microsatellite instability in the development of sporadic colorectal cancer. British journal of cancer 44 17031395
2012 MUTYH gene variants and breast cancer in a Dutch case–control study. Breast cancer research and treatment 43 22297469
2006 Duodenal carcinoma in MUTYH-associated polyposis. Journal of clinical pathology 43 16943222
2015 SIRT6 protein deacetylase interacts with MYH DNA glycosylase, APE1 endonuclease, and Rad9-Rad1-Hus1 checkpoint clamp. BMC molecular biology 41 26063178
2011 Lynch syndrome and MYH-associated polyposis: review and testing strategy. Journal of clinical gastroenterology 41 21325953
2014 MUTYH, an adenine DNA glycosylase, mediates p53 tumor suppression via PARP-dependent cell death. Oncogenesis 40 25310643
2005 A kindred with MYH-associated polyposis and pilomatricomas. American journal of medical genetics. Part A 40 15690400
2019 When you're strange: Unusual features of the MUTYH glycosylase and implications in cancer. DNA repair 39 31203172
2015 Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice. Cell reports 39 26711335
2008 Cells deficient in oxidative DNA damage repair genes Myh and Ogg1 are sensitive to oxidants with increased G2/M arrest and multinucleation. Carcinogenesis 38 18258604
2008 Genomic and functional analyses of MUTYH in Japanese patients with adenomatous polyposis. Clinical genetics 37 18422726
2005 Mutations of APC and MYH in unrelated Italian patients with adenomatous polyposis coli. Human mutation 37 16134147
2013 Coordination of MYH DNA glycosylase and APE1 endonuclease activities via physical interactions. DNA repair 35 24209961
2011 Lack of the DNA glycosylases MYH and OGG1 in the cancer prone double mutant mouse does not increase mitochondrial DNA mutagenesis. DNA repair 34 22209780
2013 Mammalian MutY homolog (MYH or MUTYH) protects cells from oxidative DNA damage. DNA repair 33 24315136
2005 Germline mutations in the MYH gene in Swedish familial and sporadic colorectal cancer. Genetic testing 33 15943555
2004 MUTYH prevents OGG1 or APEX1 from inappropriately processing its substrate or reaction product with its C-terminal domain. Nucleic acids research 33 15199168
2004 Expression of DNA repair protein: MYH, NTH1, and MTH1 in colorectal cancer. Hepato-gastroenterology 31 15143881
2017 Burden and Profile of Somatic Mutation in Duodenal Adenomas from Patients with Familial Adenomatous- and MUTYH-associated Polyposis. Clinical cancer research : an official journal of the American Association for Cancer Research 30 28790112
2007 Investigation of pathogenic mechanisms in multiple colorectal adenoma patients without germline APC or MYH/MUTYH mutations. British journal of cancer 30 17505512
2006 MUTYH and the mismatch repair system: partners in crime? Human genetics 30 16408224
2021 Monoallelic deleterious MUTYH germline variants as a driver for tumorigenesis. The Journal of pathology 29 34816434
2021 MUTYH Actively Contributes to Microglial Activation and Impaired Neurogenesis in the Pathogenesis of Alzheimer's Disease. Oxidative medicine and cellular longevity 29 34970419
2016 MUTYH promotes oxidative microglial activation and inherited retinal degeneration. JCI insight 29 27699246
2006 Implication of MYH in colorectal polyposis. Annals of surgery 29 17122612
2022 MUTYH-associated tumor syndrome: The other face of MAP. Oncogene 28 35422474
2020 Linc-MYH configures INO80 to regulate muscle stem cell numbers and skeletal muscle hypertrophy. The EMBO journal 28 32960481
2006 MutY and MutY homologs (MYH) in genome maintenance. Frontiers in bioscience : a journal and virtual library 28 16720376
2019 Multi-gene panel testing confirms phenotypic variability in MUTYH-Associated Polyposis. Familial cancer 27 30604180
2021 MUTYH as an Emerging Predictive Biomarker in Ovarian Cancer. Diagnostics (Basel, Switzerland) 26 33419231
2017 Monitoring of the spatial and temporal dynamics of BER/SSBR pathway proteins, including MYH, UNG2, MPG, NTH1 and NEIL1-3, during DNA replication. Nucleic acids research 26 28575236
2015 Functional Complementation Assay for 47 MUTYH Variants in a MutY-Disrupted Escherichia coli Strain. Human mutation 26 25820570
2015 Association between single nucleotide polymorphisms of MUTYH, hOGG1 and NEIL1 genes, and depression. Journal of affective disorders 26 26074017
2006 Novel findings in Swedish patients with MYH-associated polyposis: mutation detection and clinical characterization. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 25 16616356
2010 MYH biallelic mutation can inactivate the two genetic pathways of colorectal cancer by APC or MLH1 transversions. Familial cancer 24 20640893
2009 Hereditary colorectal cancer: MYH-associated polyposis and other newly identified disorders. Best practice & research. Clinical gastroenterology 24 19258188
2024 Pan-Cancer Interrogation of MUTYH Variants Reveals Biallelic Inactivation and Defective Base Excision Repair Across a Spectrum of Solid Tumors. JCO precision oncology 23 38394468
2022 Monoallelic MUTYH pathogenic variants ascertained via multi-gene hereditary cancer panels are not associated with colorectal, endometrial, or breast cancer. Familial cancer 23 34981295
2022 Identifying colorectal cancer caused by biallelic MUTYH pathogenic variants using tumor mutational signatures. Nature communications 23 35668106
2019 Efficacy of immune checkpoint blockade in MUTYH-associated hereditary colorectal cancer. Investigational new drugs 23 31377904
2016 Oxidized dNTPs and the OGG1 and MUTYH DNA glycosylases combine to induce CAG/CTG repeat instability. Nucleic acids research 23 26980281
2018 A human MUTYH variant linking colonic polyposis to redox degradation of the [4Fe4S]2+ cluster. Nature chemistry 22 29915346
2012 Involvement of Werner syndrome protein in MUTYH-mediated repair of oxidative DNA damage. Nucleic acids research 22 22753033
2007 MYH, OGG1, MTH1, and APC alterations involved in the colorectal tumorigenesis of Korean patients with multiple adenomas. Virchows Archiv : an international journal of pathology 22 17252231
2007 Germline mutations of the MYH gene in Korean patients with multiple colorectal adenomas. International journal of colorectal disease 22 17703316
2009 A common mutation of the MYH gene is associated with increased DNA oxidation and age-related diseases. Free radical biology & medicine 21 19932167
2007 Germline MYH mutations in a clinic-based series of Canadian multiple colorectal adenoma patients. Journal of surgical oncology 21 17219385
2021 Structure of the mammalian adenine DNA glycosylase MUTYH: insights into the base excision repair pathway and cancer. Nucleic acids research 20 34142156
2016 Genetic association of MYH genes with hereditary hearing loss in Korea. Gene 20 27393652
2015 Correlation between mutations and mRNA expression of APC and MUTYH genes: new insight into hereditary colorectal polyposis predisposition. Journal of experimental & clinical cancer research : CR 20 26511139
2013 MUTYH-associated colorectal cancer and adenomatous polyposis. Surgery today 20 23605219
2011 The genetics of familial adenomatous polyposis (FAP) and MutYH-associated polyposis (MAP). Acta gastro-enterologica Belgica 20 22103048
2021 Single molecule analysis indicates stimulation of MUTYH by UV-DDB through enzyme turnover. Nucleic acids research 19 34232996
2006 Immunohistochemical expression of MYH protein can be used to identify patients with MYH-associated polyposis. Gastroenterology 19 16890597

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