Affinage

PMS1

PMS1 protein homolog 1 · UniProt P54277

Length
932 aa
Mass
105.8 kDa
Annotated
2026-06-10
65 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PMS1 (yeast Pms1; the eukaryotic ortholog of bacterial MutL/HexB) is a core DNA mismatch repair (MMR) factor that functions as the obligate heterodimeric partner of MLH1, forming the MutLα complex that couples mismatch recognition to strand-specific excision (PMID:3896926, PMID:2676974, PMID:8066446). The heterodimer has no intrinsic affinity for mismatches but is recruited to mispaired DNA through ATP-dependent ternary complex formation with the MSH2-MSH6 and MSH2-MSH3 sliding clamps, with recruitment specificity that tracks genetic MMR specificity, and it cooperatively enhances mismatch binding by the MutS complexes (PMID:8066446, PMID:9368761, PMID:9545323, PMID:15811858, PMID:24550389). MLH1 and PMS1 each contribute distinct biochemical activities: their N-terminal domains carry independent intrinsic ATPases (ATP binding favored ~10-fold by MLH1) and DNA-binding surfaces, while the C-terminal domains form the dimerization interface and house a latent endonuclease whose active site is built from the Pms1 C-terminus together with the strictly conserved MLH1 C-terminal FERC motif (PMID:11575920, PMID:11717305, PMID:12682353, PMID:17176067, PMID:20138591, PMID:23435383, PMID:24204293). This endonuclease is activated by PCNA/RFC and, upon recruitment, nicks the newly replicated strand to initiate excision; the activity is essential, as loss of Pms1 endonuclease produces a genome-wide mutator effect equivalent to abolishing mismatch recognition itself (PMID:24981171, PMID:26170454, PMID:39016170). Mlh1-Pms1 uses ATP-driven DNA compaction to search for strand-discrimination signals, stabilizing and protecting pre-existing nicks while its MLH1-subunit ATPase promotes release from self-generated nicks, and it can drive a third, Exo1/Rad27-independent excision pathway that produces single-stranded gaps (PMID:41335467, PMID:39704127, PMID:41439704). Disruption of compatible MLH1-PMS1 interaction, or specific hPMS1 missense alleles that convert the complex into a DNA-bound roadblock, causes dominant mutator phenotypes (PMID:16492773, PMID:33303966), and Pms1 drives somatic CAG repeat expansion underlying Huntington's disease pathogenesis (PMID:39026894, PMID:38609352).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1985 Medium

    Established that PMS1 is a mismatch correction function, defining its biological role before any molecular mechanism was known.

    Evidence Genetic isolation of yeast pms1 mutants with post-meiotic segregation and mitotic mutation-avoidance defects

    PMID:3896926

    Open questions at the time
    • No molecular identity of the gene product
    • No biochemical activity defined
  2. 1989 High

    Cloning and sequencing placed PMS1 in the conserved MutL family, establishing MMR as an evolutionarily conserved pathway and pointing to a MutL-like role.

    Evidence Gene cloning, sequencing, deletion mutagenesis, and homology to bacterial MutL/HexB in yeast

    PMID:2676974

    Open questions at the time
    • Homology did not define the partner or catalytic activity
    • No protein-level interactions tested
  3. 1994 High

    Defined PMS1's molecular partner and pathway position by showing physical association with MLH1 and joint binding to MSH2-heteroduplex complexes, and that MLH1 and PMS1 act in one pathway.

    Evidence Co-immunoprecipitation/binding ternary complex assays and genetic epistasis of mlh1Δ pms1Δ double mutants in yeast

    PMID:8066446 PMID:8264608

    Open questions at the time
    • Heterodimer stoichiometry not yet resolved
    • No catalytic function identified
  4. 1997 High

    Clarified how the heterodimer engages mismatches by showing it has no intrinsic mispair affinity but cooperatively enhances MSH2-MSH3 binding.

    Evidence Purified-protein in vitro mismatch binding assays in yeast

    PMID:9368761

    Open questions at the time
    • Nucleotide dependence of recruitment not defined
    • Downstream catalytic step unknown
  5. 1998 High

    Resolved the nucleotide requirement for complex assembly and demonstrated in vivo non-redundancy among MMR MutL components.

    Evidence In vitro ternary complex assembly with ATP/ATPγS in yeast; comparative Pms1/Mlh1/Pms2 knockout mouse tumor and mutational spectra

    PMID:9500552 PMID:9545323

    Open questions at the time
    • Functional distinction between mammalian PMS1 and PMS2 not mechanistically explained
    • Catalytic role of the heterodimer still undefined
  6. 2001 High

    Defined the heterodimer's DNA-binding and ATPase architecture, showing cooperative multi-site DNA binding and asymmetric intrinsic ATPases in the Mlh1 and Pms1 NTDs.

    Evidence DNA binding assays, atomic force microscopy, ATP hydrolysis assays, and in vivo mutagenesis in yeast

    PMID:11575920 PMID:11717305

    Open questions at the time
    • Functional output of ATPase activity in repair not yet linked to a catalytic step
    • How DNA binding couples to mismatch processing unclear
  7. 2003 High

    Mapped asymmetry of DNA engagement by showing Mlh1 NTD positive residues dominate DNA binding and MMR over the homologous Pms1 residue.

    Evidence NTD-fragment DNA binding assays with site-directed mutagenesis and in vivo mutation rate assays in yeast

    PMID:12682353

    Open questions at the time
    • Structural basis of the binding surface not resolved
    • Catalytic activity still unidentified
  8. 2005 High

    Distinguished two mechanistically distinct ternary complexes (mispair-dependent sliding vs. mispair-independent end-dependent), refining the recruitment model.

    Evidence Real-time biosensor binding with reversible DNA end-blocking and ATP/ATPγS comparison in yeast

    PMID:15811858

    Open questions at the time
    • Physiological significance of the two complex types not established
    • No catalytic readout
  9. 2006 High

    Established that compatible MLH1-PMS1 interaction is essential through negative epistasis between natural alleles, and surveyed human PMS1 interactors implicating roles beyond MMR.

    Evidence Natural-strain genetic crosses and chimeric genes in yeast; large-scale co-IP/MS of human PMS1; CTD interface mapping by surface modification/MS

    PMID:16492773 PMID:17148452 PMID:17176067

    Open questions at the time
    • Non-MMR human PMS1 interactions not functionally validated
    • Dimerization interface inferred from modeling, not crystal structure at the time
  10. 2004 High

    Separated PMS1's role in mismatch correction from heteroduplex rejection, showing it is dispensable for SSA rejection but required for correcting mismatches in SSA intermediates.

    Evidence Genetic epistasis using a defined SSA divergence assay with single and triple deletion mutants in yeast

    PMID:15199178

    Open questions at the time
    • Redundancy with Mlh2/Mlh3 not fully dissected
    • Mechanism of mismatch correction within SSA not defined
  11. 2013 High

    Provided the structural and genetic basis of the endonuclease, showing the Mlh1 C-terminus completes the Pms1 active site and defining catalytic residues governing an Exo1-independent pathway.

    Evidence X-ray crystallography of the MutLα CTD with partner peptides; dominant pms1 endonuclease-dead mutation screen with in vitro nuclease assays and exo1Δ epistasis in yeast

    PMID:23435383 PMID:24204293

    Open questions at the time
    • Activation mechanism of the latent endonuclease not yet defined
    • Strand-discrimination signal recognition unresolved
  12. 2014 High

    Defined endonuclease activation and recruitment determinants, showing PCNA activates the nuclease and that MSH2-MSH3 imparts mispair specificity matching genetic MMR specificity.

    Evidence PCNA mutant genetic screen with live-cell focus imaging and epistasis; in vitro recruitment/sliding-clamp and mispair specificity assays; characterization of Mlh1-Mlh2 (PMS1 ortholog) as an accessory factor in yeast

    PMID:24550389 PMID:24811092 PMID:24981171

    Open questions at the time
    • Order and structural mechanism of PCNA-driven activation incomplete
    • How mammalian PMS1 (Mlh2 ortholog) functions as accessory factor in human cells not directly shown
  13. 2012 High

    Identified the Mlh1 disordered linker as critical for DNA binding and ternary complex formation, linking flexible regions to repair function.

    Evidence Engineered protease cleavage of the Mlh1 linker with in vitro binding and in vivo MMR assays in yeast

    PMID:22659005

    Open questions at the time
    • How the linker positions the catalytic domains not resolved
    • Conformational coupling to endonuclease unclear
  14. 2015 High

    Reconstituted Mlh1-Pms1-dependent MMR from defined components, establishing the minimal factors for endonuclease activation and complete repair.

    Evidence In vitro reconstitution with MSH2-MSH6/MSH3, PCNA, RFC, Exo1, RPA, Pol δ and active-site mutant controls in yeast

    PMID:26170454

    Open questions at the time
    • Strand-discrimination signal search mechanism not addressed
    • Coupling of compaction/ATPase to incision not yet defined
  15. 2020 High

    Defined a disease-relevant gain-of-function mechanism whereby human PMS1 missense alleles trap Mlh1-hPMS1 as a DNA roadblock that blocks MMR.

    Evidence Yeast genetic assay with human PMS1 mutations, frameshift mutator and focus-accumulation readouts, and DNA-binding suppressor analysis

    PMID:33303966

    Open questions at the time
    • Roadblock mechanism not validated in human cells
    • Native human MLH1-PMS1 catalytic role not directly tested
  16. 2021 High

    Showed that the intrinsically disordered regions must remain flexible for endonuclease control, since constraining the Mlh1 IDR abolishes MMR while inappropriate Mlh1-Pms1 IDR crosslinking activates the nuclease.

    Evidence Crosslinking MS and FRB-FKBP rapamycin-inducible dimerization with in vivo MMR and in vitro endonuclease assays in yeast

    PMID:34390347

    Open questions at the time
    • Physiological conformational trigger of activation not identified
    • Spatial arrangement during in vivo repair unknown
  17. 2024 High

    Established the quantitative importance of the Pms1 endonuclease, showing endonuclease loss is as mutagenic genome-wide as loss of mismatch recognition.

    Evidence Whole-genome sequencing of pms1-DE versus msh2Δ and polymerase mutator yeast strains

    PMID:39016170

    Open questions at the time
    • Does not resolve how the nick is targeted to the nascent strand in vivo
    • Mammalian equivalence not tested
  18. 2025 High

    Defined the strand-discrimination search and nick-handling mechanism, showing ATP-driven DNA compaction locates nicks, Mlh1 ATPase releases the complex from self-generated nicks, and the endonuclease drives a third Exo1/Rad27-independent excision pathway.

    Evidence In vitro reconstitution with phased nicking, ATP-dependent compaction, RFC/PCNA competition, exonuclease protection, and gap analysis using ATPase/endonuclease-mutant variants in yeast

    PMID:39704127 PMID:41335467 PMID:41439704

    Open questions at the time
    • In vivo timing of nick encounter relative to RFC/PCNA not directly observed
    • How compaction reads genuine strand-discrimination signals in chromatin unknown
  19. 2024 Medium

    Linked PMS1 to repeat-expansion disease, establishing it as a driver of somatic CAG expansion in Huntington's disease models.

    Evidence Pms1 knockout in Q140 HD knock-in mice with single-nucleus CAG sequencing (preprint); CRISPR and splice-modulation of PMS1 in RPE1 HTT CAG-expansion cell models

    PMID:38609352 PMID:39026894

    Open questions at the time
    • Molecular mechanism linking MMR endonuclease activity to expansion not resolved
    • Dosage threshold (homozygous vs. heterozygous) mechanism unclear
  20. 2023 Low

    Raised the possibility of regulatory phosphorylation of PMS1 by CDK2 at Thr331 as a meiotic input.

    Evidence In vitro kinase assay with in silico substrate prediction

    PMID:36952545

    Open questions at the time
    • In vitro phosphorylation only; not validated in vivo
    • Functional consequence on MMR complex assembly not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the catalytic and strand-discrimination mechanisms defined in yeast operate for the human MLH1-PMS1 complex, including its precise role in somatic CAG repeat expansion, remains to be established.
  • Human MLH1-PMS1 endonuclease activity not directly characterized in the corpus
  • Mechanism connecting PMS1 function to repeat expansion in human neurons undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0140097 catalytic activity, acting on DNA 6 GO:0016787 hydrolase activity 4 GO:0060089 molecular transducer activity 4 GO:0140657 ATP-dependent activity 3
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-73894 DNA Repair 5 R-HSA-1643685 Disease 3
Partners
EXO1MLH1MSH2MSH3MSH6PCNARFC
Complex memberships
MutLα (MLH1-PMS1 / Mlh1-Pms1 heterodimer)

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1985 PMS1 (yeast) is required for post-meiotic segregation correction and mitotic mutation avoidance, identifying it as a mismatch correction function acting on heteroduplex DNA intermediates during recombination and replication. Genetic isolation and characterization of pms1 mutants; meiotic and mitotic phenotype analysis Genetics Medium 3896926
1989 The yeast PMS1 gene encodes a 103 kDa protein with sequence homology to bacterial MutL and HexB, establishing an evolutionary conserved role in DNA mismatch repair across prokaryotes and eukaryotes. Cloning, nucleotide sequencing, deletion mutagenesis, sequence alignment Journal of bacteriology High 2676974
1994 Yeast MLH1 and PMS1 physically associate (possibly forming a heterodimer) and act in concert to bind an MSH2-heteroduplex complex containing a G-T mismatch, forming a ternary complex during initiation of DNA mismatch repair. Physical interaction assays (co-immunoprecipitation/binding studies), heteroduplex binding assays Science High 8066446
1994 MLH1 and PMS1 act in the same DNA mismatch repair pathway in yeast; the mlh1Δ pms1Δ double mutant is indistinguishable from either single mutant, indicating they function in the same pathway. Genetic epistasis analysis; spontaneous mutation rate assays; meiotic phenotype analysis of single and double mutants Molecular and cellular biology High 8264608
1997 The purified yeast MLH1-PMS1 heterodimer alone has no affinity for mismatched DNA but greatly enhances mismatch binding by the MSH2-MSH3 complex, indicating a cooperative role in mismatch recognition. Protein purification to near homogeneity; in vitro mismatch binding assays Current biology High 9368761
1998 The yeast MSH2-MSH6 and MLH1-PMS1 complexes form a ternary complex on mismatch-containing DNA; this formation requires ATP (or ATPγS), indicating ATP binding (not hydrolysis) by MSH2-MSH6 induces a conformation competent for MLH1-PMS1 interaction. Protein purification; in vitro ternary complex assembly assays with ATP and ATPγS; gel-shift/binding assays The Journal of biological chemistry High 9545323
1998 Mice deficient for Pms1 show different tumor susceptibilities and mutational spectra from Mlh1- and Pms2-deficient mice, indicating that although these MMR genes share overlapping functions, they are not identical in vivo. Gene knockout mouse models; tumor incidence and mutational spectrum analysis Nature genetics High 9500552
2001 The yeast Mlh1-Pms1 heterodimer is a DNA-binding protein that binds short DNA substrates with low affinity but displays high-affinity cooperative binding to duplex DNA >241 bp, with more than one DNA binding site on the heterodimer; atomic force microscopy shows simultaneous interaction with two different DNA regions. DNA binding assays (biosensor, filter binding); atomic force microscopy; competition assays Journal of molecular biology High 11575920
2001 The N-terminal domains of yeast Mlh1 and Pms1 each possess independent, intrinsic ATPase activities; Mlh1 NTD binds ATP with >10-fold higher affinity than Pms1 NTD; mutations in conserved ATP-binding sites reduce ATP binding, hydrolysis, and MMR in vivo, consistent with a model where ATP binding (primarily to Mlh1) modulates MMR protein interactions. ATP hydrolysis assays; limited proteolysis protection; equilibrium dialysis; in vivo mutagenesis The Journal of biological chemistry High 11717305
2001 PMS1 is cleaved by granzyme B, and autoantibodies to PMS1 are found in myositis patients but not in other autoimmune diseases, identifying PMS1 as a myositis-specific autoantigen targeted as a granzyme B substrate. Immunoprecipitation; granzyme B cleavage assays; patient serology Arthritis and rheumatism Medium 11229471
2003 The N-terminal domains (NTDs) of yeast Mlh1 and Pms1 independently bind double-stranded and single-stranded DNA; conserved positively charged residues in the Mlh1 NTD are important for DNA binding and MMR in vivo, whereas the homologous Pms1 residue has smaller effects, indicating Mlh1 and Pms1 differ in their interactions with DNA. DNA binding assays with NTD fragments; site-directed mutagenesis; in vivo mutation rate assays Nucleic acids research High 12682353
2004 Pms1 (yeast) is not required for heteroduplex rejection during single-strand annealing; deletion of PMS1, MLH2, or MLH3 individually had no effect on rejection, but a pms1Δ mlh2Δ mlh3Δ triple mutant resembled mlh1Δ. However, correction of mismatches within SSA heteroduplex intermediates requires PMS1 and MLH1. Genetic epistasis using SSA assay with defined sequence divergence; deletion mutant analysis Proceedings of the National Academy of Sciences of the United States of America High 15199178
2005 The MLH1-PMS1 complex forms both mispair-dependent and mispair-independent ternary complexes with MSH2-MSH6 on DNA; mispair-dependent complexes require ATP and Mg2+ and dissociate via DNA ends (consistent with sliding), while mispair-independent complexes require free DNA ends and dissociate directly. Real-time biosensor binding assays with reversible DNA end-blocking system; ATP and ATPγS comparisons The Journal of biological chemistry High 15811858
2006 Negative epistasis between naturally occurring S288c MLH1 and SK1 PMS1 alleles (a single amino acid polymorphism in each gene) causes a mismatch repair defect, establishing that compatible MLH1-PMS1 interaction is essential for MMR function. Genetic analysis of natural strain crosses; chimeric gene construction; mutator assays Proceedings of the National Academy of Sciences of the United States of America High 16492773
2006 Human PMS1 interacts with MLH1 and additional proteins identified by large-scale immunoprecipitation and mass spectrometry, implicating PMS1 in processes beyond MMR including intracellular transport, cell signaling, recombination, and ubiquitylation. Large-scale immunoprecipitation; mass spectrometric analysis of co-purified proteins The Journal of biological chemistry Medium 17148452
2006 The C-terminal dimerization interface of the yeast MLH1-PMS1 heterodimer involves Lys665, Lys675, and Lys704 of MLH1, identified by protein surface modification and mass spectrometry as residues buried upon heterodimer formation. Protein surface modification; mass spectrometry; secondary structure prediction and homology modeling Biochemistry Medium 17176067
2010 The 2.5 Å crystal structure of the yeast Pms1 N-terminal domain reveals conserved positively charged surface residues that contribute to DNA binding and MMR; two glutamate substitutions reduced DNA binding affinity in vitro and increased mutation rates in vivo, and other surface residue substitutions caused mutator phenotypes without affecting DNA binding, implying interactions with other MMR proteins. X-ray crystallography; site-directed mutagenesis; in vitro DNA binding assays; in vivo mutation rate assays DNA repair High 20138591
2011 Mass spectrometry footprinting of yeast Pms1 NTD identified specific residues along a positively charged groove as the DNA-binding interface; both DNA and non-hydrolyzable ATP analog stabilize the Pms1 NTD in a similar conformation. Limited proteolysis; oxidative surface mapping; mass spectrometry; structural modeling DNA repair Medium 21354867
2012 The unstructured linker arm of Mlh1 (but less so Pms1) is critical for DNA binding by Mlh1-Pms1 and for ternary complex formation with Msh2-Msh6 on mismatch DNA; protease cleavage of the Mlh1 linker causes a complete MMR defect in vivo. Engineered protease cleavage site in Mlh1 linker; in vitro DNA binding; in vivo MMR assays; truncation series Journal of molecular biology High 22659005
2013 Crystal structures of the yeast MutLα (Mlh1-Pms1) C-terminal domain reveal that the strictly conserved C-terminus of Mlh1 forms part of the Pms1 endonuclease active site; structures also reveal binding mode of the MIP-box motif shared by Mlh1 partners Exo1 and Ntg2. X-ray crystallography of CTD alone and in complex with partner peptides; structural comparison with bacterial MutL Nature structural & molecular biology High 23435383
2013 Six dominant pms1 mutations (including pms1-G683E, -C817R, -C848S, -H850R, -H703A, -E707A) specifically inactivate the Mlh1-Pms1 endonuclease active site and define a Exo1-independent MMR pathway; the Mlh1-FERC motif contributes to the endonuclease active site. Dominant mutation screen; molecular modeling; in vitro endonuclease activity assays; genetic epistasis with exo1Δ PLoS genetics High 24204293
2014 PCNA activates the Mlh1-Pms1 endonuclease in an Exo1-independent MMR pathway; specific PCNA mutations disrupt either Msh2-Msh6 binding or Mlh1-Pms1 endonuclease activation, and the latter class causes hyperaccumulation of Mlh1-Pms1 repair foci. Genetic screen for PCNA mutants; live-cell imaging of Mlh1-Pms1 foci; genetic epistasis; in vivo mutation rate assays Molecular cell High 24981171
2014 Mlh1-Pms1 is recruited to mispair-containing DNA by Msh2-Msh3 on +1 to +4 insertion/deletions and CC, AA, and GG mispairs; the mispair specificity of Mlh1-Pms1 recruitment correlates best with genetic MMR specificity data. In vitro recruitment/sliding clamp assays; mispair binding assays; chimeric/mutant Msh2-Msh3 protein analysis The Journal of biological chemistry High 24550389
2014 Mlh1-Mlh2 (S. cerevisiae; the yeast ortholog of mammalian PMS1) is an accessory factor that forms MMR foci dependent on Msh2-Msh6, is recruited to mispair-containing DNA in vitro by Msh2-Msh6 or Msh2-Msh3, and acts to enhance Mlh1-Pms1 activity; its deletion causes synergistic mutation rate increases with MSH6 deletion or reduced Pms1 expression. Live-cell imaging; in vitro recruitment assays; genetic epistasis; mutation rate assays; phylogenetic analysis PLoS genetics High 24811092
2015 Reconstitution of Mlh1-Pms1-dependent MMR in vitro requires Msh2-Msh6 (or Msh2-Msh3), PCNA, and RFC for endonuclease activation, and additionally Exo1, RPA, RFC, PCNA, and DNA polymerase δ for complete MMR; both reactions require a functional Mlh1-Pms1 endonuclease active site and mispair recognition but not sliding clamp formation. In vitro reconstitution of MMR; endonuclease activation assays; mutagenesis of active-site residues The Journal of biological chemistry High 26170454
2020 Specific missense mutations in human hPMS1 (homologous to yeast Mlh2) confer a dominant mutator phenotype by causing Mlh1-hPMS1 complexes to act as roadblocks on DNA, preventing MMR; this effect is suppressed by mutations that prevent DNA binding. Yeast genetic assay for dominant mutations; frameshift mutation rate assays; MMR focus accumulation imaging; DNA-binding suppressor analysis Communications biology High 33303966
2021 Conditional cross-linking of the intrinsically disordered regions (IDRs) of Mlh1-Pms1 using FRB-FKBP rapamycin-induced dimerization shows that constraining the Mlh1 IDR causes a complete MMR defect and inhibits Mlh1-Pms1 endonuclease activity; cross-linking of the Mlh1 and Pms1 IDRs to each other inappropriately activates the endonuclease. Cross-linking mass spectrometry; FRB-FKBP rapamycin-inducible dimerization; in vivo MMR assays; in vitro endonuclease assays Nucleic acids research High 34390347
2023 CDK2 phosphorylates PMS1 at Thr331 in vitro, identifying PMS1 as a potential meiotic CDK2 substrate; the functional consequence on MMR complex assembly was not conclusively established. In vitro kinase assay; in silico substrate prediction PloS one Low 36952545
2024 Loss of Pms1 endonuclease activity (pms1-DE variant) causes strong mutator effects throughout the yeast genome for all substitution types and indels, and its effect is equivalent to loss of initial mismatch recognition (msh2Δ), establishing that strand discrimination via the Pms1 endonuclease is as important for MMR as mismatch recognition. Whole-genome sequencing of yeast mutants; mutation spectrum and rate analysis; pms1-DE compared to msh2Δ and polymerase mutator combinations Nucleic acids research High 39016170
2024 Pms1 (yeast) drives somatic CAG repeat expansion in Huntington's disease model mice; homozygous Pms1 knockout strongly reduces CAG repeat migration rate in Q140 striatal MSNs, and together with Msh3 sets the linear rate of neuronal CAG expansion driving mHtt-dependent pathogenesis. Pms1 knockout crossed to Q140 HD knock-in mice; single-nucleus CAG-repeat sequencing; quantitative repeat migration rate analysis bioRxivpreprint Medium 39026894
2024 Splice modulation of PMS1 (promoting pseudoexon inclusion and reducing PMS1 expression) reduces somatic HTT CAG repeat expansion in an engineered cell model; homozygous but not heterozygous PMS1 inactivation also reduces expansion, supporting PMS1 as a driver of somatic repeat instability. CRISPR-Cas9 editing of PMS1; splice modulator treatment; CAG repeat expansion assays in RPE1 cells Nature communications High 38609352
2025 Mlh1-Pms1 uses ATP to compact continuous DNA (a proposed search mechanism for strand-discrimination signals); upon encountering a pre-existing nick, compaction is suppressed and the complex stabilizes the nick, protecting it from RFC/PCNA-induced melting; timing of nick encounter relative to RFC/PCNA determines whether endonuclease is activated. In vitro reconstitution; phased nicking assays; ATP-dependent DNA compaction assays; RFC/PCNA competition assays Nucleic acids research High 41335467
2025 Mlh1-Pms1 ATPase activity in the Mlh1 subunit promotes disengagement from self-generated nicks; ATPase-deficient variant becomes trapped on its own endonuclease products; Mlh1-Pms1 also selectively protects pre-existing nicks from exonuclease degradation, suggesting two distinct modes of action on self-generated versus pre-existing nicks. In vitro endonuclease and ATPase assays with ATP-binding/hydrolysis-deficient Mlh1-Pms1 variants; exonuclease protection assays Nucleic acids research High 39704127
2025 Reconstituted MMR using Mlh1-Pms1 endonuclease activity (without Exo1, Rad27, or strand-displacement synthesis) proceeds via nicked-strand-specific excision forming single-strand DNA gaps of broad size range; this establishes a third redundant excision pathway in eukaryotic MMR. In vitro reconstitution of MMR with defined purified proteins; gap analysis; active-site mutant controls Proceedings of the National Academy of Sciences of the United States of America High 41439704

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DNA mismatch repair. Nature genetics 311 9500552
1994 MLH1, PMS1, and MSH2 interactions during the initiation of DNA mismatch repair in yeast. Science (New York, N.Y.) 292 8066446
1985 Meiotic gene conversion mutants in Saccharomyces cerevisiae. I. Isolation and characterization of pms1-1 and pms1-2. Genetics 216 3896926
1994 Dual requirement in yeast DNA mismatch repair for MLH1 and PMS1, two homologs of the bacterial mutL gene. Molecular and cellular biology 203 8264608
1989 Cloning and nucleotide sequence of DNA mismatch repair gene PMS1 from Saccharomyces cerevisiae: homology of PMS1 to procaryotic MutL and HexB. Journal of bacteriology 201 2676974
2004 Heteroduplex rejection during single-strand annealing requires Sgs1 helicase and mismatch repair proteins Msh2 and Msh6 but not Pms1. Proceedings of the National Academy of Sciences of the United States of America 174 15199178
2006 Characterization of the interactome of the human MutL homologues MLH1, PMS1, and PMS2. The Journal of biological chemistry 126 17148452
1998 ATP-dependent assembly of a ternary complex consisting of a DNA mismatch and the yeast MSH2-MSH6 and MLH1-PMS1 protein complexes. The Journal of biological chemistry 109 9545323
2005 Analysis of the interaction between the Saccharomyces cerevisiae MSH2-MSH6 and MLH1-PMS1 complexes with DNA using a reversible DNA end-blocking system. The Journal of biological chemistry 106 15811858
2013 Structure of the MutLα C-terminal domain reveals how Mlh1 contributes to Pms1 endonuclease site. Nature structural & molecular biology 100 23435383
2014 PCNA and Msh2-Msh6 activate an Mlh1-Pms1 endonuclease pathway required for Exo1-independent mismatch repair. Molecular cell 89 24981171
2001 High affinity cooperative DNA binding by the yeast Mlh1-Pms1 heterodimer. Journal of molecular biology 80 11575920
1997 Enhancement of MSH2-MSH3-mediated mismatch recognition by the yeast MLH1-PMS1 complex. Current biology : CB 76 9368761
1990 Mismatch repair-induced meiotic recombination requires the pms1 gene product. Genetics 74 2179055
2006 Negative epistasis between natural variants of the Saccharomyces cerevisiae MLH1 and PMS1 genes results in a defect in mismatch repair. Proceedings of the National Academy of Sciences of the United States of America 70 16492773
1994 Cloning, characterization and chromosomal assignment of the human genes homologous to yeast PMS1, a member of mismatch repair genes. Biochemical and biophysical research communications 69 7980603
1999 Involvement of nucleotide-excision repair in msh2 pms1-independent mismatch repair. Nature genetics 65 10080187
2001 Differential ATP binding and intrinsic ATP hydrolysis by amino-terminal domains of the yeast Mlh1 and Pms1 proteins. The Journal of biological chemistry 61 11717305
1989 Nucleotide sequence of the Streptococcus pneumoniae hexB mismatch repair gene: homology of HexB to MutL of Salmonella typhimurium and to PMS1 of Saccharomyces cerevisiae. Journal of bacteriology 59 2676973
2013 Dominant mutations in S. cerevisiae PMS1 identify the Mlh1-Pms1 endonuclease active site and an exonuclease 1-independent mismatch repair pathway. PLoS genetics 55 24204293
2003 DNA binding by yeast Mlh1 and Pms1: implications for DNA mismatch repair. Nucleic acids research 49 12682353
2001 The DNA mismatch repair enzyme PMS1 is a myositis-specific autoantigen. Arthritis and rheumatism 48 11229471
2014 Mispair-specific recruitment of the Mlh1-Pms1 complex identifies repair substrates of the Saccharomyces cerevisiae Msh2-Msh3 complex. The Journal of biological chemistry 41 24550389
1989 Nucleotide sequence of the Salmonella typhimurium mutL gene required for mismatch repair: homology of MutL to HexB of Streptococcus pneumoniae and to PMS1 of the yeast Saccharomyces cerevisiae. Journal of bacteriology 40 2676972
2004 A role for the MutL homologue MLH2 in controlling heteroduplex formation and in regulating between two different crossover pathways in budding yeast. Cytogenetic and genome research 38 15467363
1996 Homologous and homeologous intermolecular gene conversion are not differentially affected by mutations in the DNA damage or the mismatch repair genes RAD1, RAD50, RAD51, RAD52, RAD54, PMS1 and MSH2. Genetics 37 8725224
2014 Mlh2 is an accessory factor for DNA mismatch repair in Saccharomyces cerevisiae. PLoS genetics 36 24811092
2002 DNA binding properties of the yeast Msh2-Msh6 and Mlh1-Pms1 heterodimers. Biological chemistry 34 12222686
2015 Activation of Saccharomyces cerevisiae Mlh1-Pms1 Endonuclease in a Reconstituted Mismatch Repair System. The Journal of biological chemistry 32 26170454
2012 The unstructured linker arms of Mlh1-Pms1 are important for interactions with DNA during mismatch repair. Journal of molecular biology 32 22659005
2024 Splice modulators target PMS1 to reduce somatic expansion of the Huntington's disease-associated CAG repeat. Nature communications 30 38609352
2001 Identification of an 85-kb DNA fragment containing pms1, a locus for photoperiod-sensitive genic male sterility in rice. Molecular genetics and genomics : MGG 28 11683269
1997 Mismatch repair in Schizosaccharomyces pombe requires the mutL homologous gene pms1: molecular cloning and functional analysis. Genetics 26 9258673
1998 Schizosaccharomyces pombe exo1 is involved in the same mismatch repair pathway as msh2 and pms1. Current genetics 25 9871115
1990 Multiple proteins bind to the P2 promoter region of the zein gene pMS1 of maize. Molecular & general genetics : MGG 25 2370845
2010 Functional residues on the surface of the N-terminal domain of yeast Pms1. DNA repair 24 20138591
2002 Alleles of the yeast Pms1 mismatch-repair gene that differentially affect recombination- and replication-related processes. Genetics 23 12454061
2001 Efficient incorporation of large (>2 kb) heterologies into heteroduplex DNA: Pms1/Msh2-dependent and -independent large loop mismatch repair in Saccharomyces cerevisiae. Genetics 19 11290705
2005 Novel PMS1 alleles preferentially affect the repair of primer strand loops during DNA replication. Molecular and cellular biology 18 16227575
1999 Analysis of yeast pms1, msh2, and mlh1 mutators points to differences in mismatch correction efficiencies between prokaryotic and eukaryotic cells. Molecular & general genetics : MGG 18 10394915
2018 Associations of Genetic Variations in Mismatch Repair Genes MSH3 and PMS1 with Acute Adverse Events and Survival in Patients with Rectal Cancer Receiving Postoperative Chemoradiotherapy. Cancer research and treatment 14 30590005
1997 Decreased expression of MLH1, MSH2, PMS1 and PMS2 in pigmented lesions indicates accumulation of failed DNA repair along with malignant transformation and tumour progression. Oncology reports 14 21590118
1994 Mutagenesis of yeast MW104-1B strain has identified the uncharacterized PMS6 DNA mismatch repair gene locus and additional alleles of existing PMS1, PMS2 and MSH2 genes. Mutation research 12 7521009
2018 Incompatibilities in Mismatch Repair Genes MLH1-PMS1 Contribute to a Wide Range of Mutation Rates in Human Isolates of Baker's Yeast. Genetics 11 30348651
2006 Mapping the dimer interface in the C-terminal domains of the yeast MLH1-PMS1 heterodimer. Biochemistry 10 17176067
2019 GNAQ and PMS1 Mutations Associated with Uveal Melanoma, Ocular Surface Melanosis, and Nevus of Ota. Ocular oncology and pathology 9 31367589
2011 Modeling of the DNA-binding site of yeast Pms1 by mass spectrometry. DNA repair 9 21354867
2011 Fine mapping and candidate gene prediction of the photoperiod and thermo-sensitive genic male sterile gene pms1(t) in rice. Journal of Zhejiang University. Science. B 9 21634036
2021 Handcuffing intrinsically disordered regions in Mlh1-Pms1 disrupts mismatch repair. Nucleic acids research 8 34390347
2020 Identification of MLH2/hPMS1 dominant mutations that prevent DNA mismatch repair function. Communications biology 8 33303966
2014 Genome-wide association study identifies variants in PMS1 associated with serum ferritin in a Chinese population. PloS one 8 25162662
2024 Instability throughout the Saccharomyces cerevisiae genome resulting from Pms1 endonuclease deficiency. Nucleic acids research 7 39016170
2020 Identification of a novel germline frameshift mutation p.D300fs of PMS1 in a patient with hepatocellular carcinoma: A case report and literature review. Medicine 7 32000458
2024 Msh3 and Pms1 Set Neuronal CAG-repeat Migration Rate to Drive Selective Striatal and Cortical Pathogenesis in HD Mice. bioRxiv : the preprint server for biology 6 39026894
2025 Mlh1-Pms1 ATPase activity is regulated distinctly by self-generated nicks and strand discrimination signals in mismatch repair. Nucleic acids research 5 39704127
2022 CMMRD caused by PMS1 mutation in a sudanese consanguineous family. Hereditary cancer in clinical practice 5 35428304
2023 Thyroid Cancer, Neuroendocrine Tumor, Adrenal Adenoma, and Other Tumors in a Patient With a Germline PMS1 Mutation. Journal of the Endocrine Society 4 37143695
2022 Analysis of the MLH1, MLH2, MLH6, PMS2 genes and their correlations with clinical data in rectal mucinous adenocarcinoma. Annali italiani di chirurgia 3 34807001
2021 Investigation of discordant sibling pairs from hereditary breast cancer families and analysis of a rare PMS1 variant. Cancer genetics 3 34852986
2024 The Mlh1-Pms1 endonuclease uses ATP to preserve DNA discontinuities as strand discrimination signals to facilitate mismatch repair. bioRxiv : the preprint server for biology 2 38915520
2023 PMS1 as a target for splice modulation to prevent somatic CAG repeat expansion in Huntington's disease. bioRxiv : the preprint server for biology 2 37547003
2025 Mlh1-Pms1 couples ATP-driven DNA compaction with nick-dependent endonuclease activation. Nucleic acids research 1 41335467
2025 DNA mismatch repair mediated by Mlh1-Pms1 endonuclease-catalyzed mispair excision. Proceedings of the National Academy of Sciences of the United States of America 1 41439704
2023 Identification PMS1 and PMS2 as potential meiotic substrates of CDK2 activity. PloS one 1 36952545
2025 The mismatch repair factor Mlh1-Pms1 uses ATP to compact and remodel DNA. bioRxiv : the preprint server for biology 0 39868200

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