Affinage

PMS2

Mismatch repair endonuclease PMS2 · UniProt P54278

Length
862 aa
Mass
95.8 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PMS2 is the catalytic partner of the MutLα heterodimer in DNA mismatch repair, correcting DNA replication slippage errors and thereby suppressing microsatellite instability and tumorigenesis (PMID:7628019, PMID:9096356). It dimerizes with MLH1 through C-terminal interactions that both stabilize PMS2 steady-state levels and unmask the nuclear localization signals required for nuclear import of the complex, with the higher-affinity MLH1 NLS providing dominant, redundant import activity (PMID:12697830, PMID:16338176, PMID:29175432). Within MutLα, PMS2 contributes a GHL ATPase domain — structurally active as a monomer but modulated within the heterodimer — whose ATP hydrolysis is required alongside that of MLH1 for repair (PMID:11574484, PMID:11897781), and a latent C-terminal endonuclease (catalytic residue E702) that is activated upon PCNA binding to its 721QRLIAP motif; this PCNA interaction couples endonuclease and ATPase activation to repair function (PMID:20624957, PMID:28439008). The endonuclease activity is specifically essential for genome maintenance, tumor suppression, and class-switch recombination but dispensable for somatic hypermutation and spermatogenesis (PMID:20624957). Beyond canonical repair, PMS2 shapes somatic hypermutation by processing tandem mispairs and, with MLH1, providing nicking activity that cooperates with uracil glycosylases to generate A-T mutations (PMID:9618520, PMID:28283534), promotes endonuclease-dependent resolution of homologous recombination intermediates in somatic cells (PMID:33453991), and suppresses GAA·TTC trinucleotide repeat expansion in neuronal tissues (PMID:23071719). PMS2 also drives DNA-damage-induced apoptosis: it interacts with and stabilizes p73 to mediate cisplatin-triggered, p73-dependent apoptosis, and contributes to alkylating-agent and ionizing-radiation killing through pathways that are at least partly p53-independent (PMID:12601175, PMID:10987303, PMID:12967659).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1995 High

    Established PMS2 as a bona fide in vivo mismatch repair factor by showing its loss produces a mutator phenotype, cancer, and meiotic defects — defining the biological stakes of the gene.

    Evidence Pms2-null mouse knockout with microsatellite instability, tumor, and spermatogenesis analysis

    PMID:7628019

    Open questions at the time
    • Did not resolve which biochemical activity of PMS2 underlies repair
    • Mechanism of the meiotic synapsis defect not defined
  2. 1997 High

    Quantified and characterized the mutator spectrum, showing PMS2 corrects replication-slippage insertion/deletion errors at repeat sequences.

    Evidence Lambda phage shuttle vector mutation reporter assay with sequencing in Pms2-/- mice

    PMID:9096356

    Open questions at the time
    • Did not establish the molecular step at which PMS2 acts in the repair reaction
  3. 1998 High

    Extended PMS2 function beyond simple replication errors to immunoglobulin diversification, defining a PMS2-dependent pathway for repairing tandem mispairs during hypermutation.

    Evidence Ig variable gene sequencing and biochemical tandem-mispair repair assay in Pms2-/- cells

    PMID:9618520

    Open questions at the time
    • Did not identify the PMS2 enzymatic activity responsible for tandem mispair processing
  4. 1999 High

    Resolved the genetic hierarchy of MutLα subunits, showing MLH1 stabilizes PMS2 and that MLH1 loss subsumes PMS2 loss for the mutator phenotype.

    Evidence Genetic epistasis with single and double knockout mice plus Western blot of protein levels

    PMID:10359802

    Open questions at the time
    • Did not address non-MMR roles where PMS2 might act independently
  5. 2000 High

    Separated PMS2's DNA-damage apoptotic signaling from the p53 pathway, showing IR-induced apoptosis acts through a distinct PMS2-dependent route.

    Evidence Apoptosis and clonogenic survival after IR in Pms2-/-, p53-/-, and double-null fibroblasts

    PMID:10987303

    Open questions at the time
    • Did not identify the PMS2 effector mediating p53-independent apoptosis
  6. 2001 High

    Provided the structural basis of the PMS2 ATPase, defining it as a GHL ATPase active as a monomer and predicting modulation by MLH1.

    Evidence X-ray crystallography of the N-terminal ATPase fragment with ATPase and DNA-binding assays

    PMID:11574484

    Open questions at the time
    • Did not test ATPase behavior in the context of full-length MutLα
    • C-terminal endonuclease not yet structurally defined
  7. 2002 High

    Demonstrated that ATP hydrolysis by both subunits is jointly required for MutLα repair and that MLH1 dominates the ATP-driven conformational cycle.

    Evidence In vitro repair reconstitution with ATPase-dead E→A mutants and limited proteolysis

    PMID:11897781

    Open questions at the time
    • Did not connect ATPase cycling to endonuclease incision
    • Coupling to downstream repair factors unresolved
  8. 2003 Medium

    Identified p73 as a direct PMS2 partner linking the protein to cisplatin-induced apoptosis, and defined dimerization-dependent nuclear import of MutLα.

    Evidence Co-IP, subcellular fractionation, cisplatin assays, and NLS mutagenesis in MMR-deficient cells

    PMID:12601175 PMID:12697830

    Open questions at the time
    • p73 interaction shown by single-lab Co-IP without structural mapping
    • Did not quantify relative NLS contributions of each subunit
  9. 2005 High

    Defined MLH1's CTH domain as essential for PMS2 stabilization and MutLα formation, established p53 as a transcriptional regulator of PMS2, and revealed MLH3/PMS2 functional redundancy.

    Evidence CTH-truncation transfection with Co-IP and survival assays; ChIP/reporter for p53 response elements; Mlh3-/-;Pms2-/- double-knockout phenotyping

    PMID:15781865 PMID:16204034 PMID:16338176

    Open questions at the time
    • Mechanism of MLH3/PMS2 substrate division not defined
    • Did not determine when p53-driven PMS2 induction is physiologically engaged
  10. 2008 Medium

    Linked a specific PMS2 polymorphism (R20Q) to loss of the p73-dependent cisplatin apoptotic function, separating this activity from canonical repair.

    Evidence Complementation of Pms2-/- fibroblasts with PMS2(R20Q) vs. wild-type, with apoptosis and survival readouts

    PMID:18768816

    Open questions at the time
    • Single-lab functional assay
    • Did not test R20Q in mismatch repair directly
  11. 2010 High

    Definitively assigned PMS2's endonuclease (E702) to genome maintenance, tumor suppression and class switch recombination while excluding it from somatic hypermutation and spermatogenesis.

    Evidence Endonuclease-dead Pms2E702K knock-in mice with in vivo mutation, CSR/SHM, tumor, and fertility readouts

    PMID:20624957

    Open questions at the time
    • Did not define the activating signal for the latent endonuclease in vivo
  12. 2017 High

    Identified PCNA binding to the PMS2 721QRLIAP motif as the activator of both endonuclease and ATPase activity, and structurally defined NLS recognition by importin-α.

    Evidence In vitro interaction/mutagenesis with repair and endonuclease reconstitution plus yeast genetics; importin-α/NLS crystallography and ITC

    PMID:28439008 PMID:29175432

    Open questions at the time
    • Did not define spatial coupling of PCNA loading to incision strand choice in vivo
  13. 2017 Medium

    Showed that PMS2/MLH1 nicking activity cooperates with uracil glycosylases to generate A-T mutations during somatic hypermutation, defining the upstream nick source.

    Evidence Ig mutation spectrum analysis in Ung-/-;Pms2 and triple-glycosylase mutant mice with cell-cycle staging

    PMID:28283534

    Open questions at the time
    • Single-lab epistasis
    • Direct biochemical demonstration of nick-to-synthesis hand-off not provided
  14. 2020 High

    Established a non-meiotic role for PMS2 endonuclease in resolving homologous recombination intermediates, partially overlapping with MLH3 and substitutable by an HJ resolvase.

    Evidence Endonuclease-dead knock-in human B cells with heteroallelic HR, Rad51 foci, SCE assays, and Gen1 rescue

    PMID:33453991

    Open questions at the time
    • Single-lab study
    • Precise HR substrate cleaved by PMS2 not biochemically defined
  15. 2012 Medium

    Revealed a tissue-specific role for PMS2 in suppressing GAA·TTC repeat expansion in post-mitotic neurons, antagonizing MutSα-driven instability.

    Evidence Somatic instability analysis of expanded (GAA·TTC)n in Pms2-/- mice carrying the human FXN locus across tissues

    PMID:23071719

    Open questions at the time
    • Mechanism of neuron-specific antagonism unresolved
    • Did not determine whether endonuclease activity is required
  16. 2016 Medium

    Implicated MLH1/PMS2 in a damage response to aberrant nucleotides, mediating dITP-induced growth arrest and strand breaks through p53.

    Evidence ITPA-deficient cell analysis with MLH1/PMS2 knockdown and p53/p21 and single-strand-break readouts

    PMID:27618981

    Open questions at the time
    • Single-lab knockdown study
    • Direct PMS2 action on dITP-containing DNA not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PMS2's distinct activities (endonuclease, ATPase, p73-apoptotic signaling) are partitioned and regulated across MMR, recombination, immunoglobulin diversification, and neuronal repeat suppression in vivo remains unresolved.
  • No unified structural model of full-length activated MutLα
  • Effector linking PMS2 to p53-independent apoptosis unidentified
  • Determinants of tissue-specific repeat suppression unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 3 GO:0016787 hydrolase activity 2 GO:0140657 ATP-dependent activity 2 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3
Partners
GSK-3BMLH1P73PCNA
Complex memberships
MutLalpha (MLH1-PMS2)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Crystal structures of the N-terminal 40 kDa ATPase fragment of human PMS2 (NhPMS2) were solved at 1.95 Å, revealing it is a GHL ATPase active as a monomer in both ATP hydrolysis and DNA binding — unlike bacterial MutL which requires dimerization. This suggests PMS2 ATPase activity may be modulated by MLH1 within MutLα. X-ray crystallography (apo, ATPγS, and ADP complexes) with biochemical ATPase and DNA-binding assays The EMBO journal High 11574484
2002 ATP hydrolysis by both MLH1 and PMS2 subunits is required for MutLα mismatch repair activity in vitro. Mutation of the catalytic glutamate in either subunit partially reduces repair; the double mutant abolishes it. MLH1 undergoes a more pronounced ATP-induced conformational change and binds ATP with higher affinity than PMS2. In vitro mismatch repair assay with purified ATPase-dead mutant MutLα proteins (E→A substitutions); limited proteolysis to monitor conformational changes The Journal of biological chemistry High 11897781
2003 PMS2 physically interacts with the p53-family transcription factor p73. This interaction stabilizes p73 and redistributes PMS2 to the nuclear compartment. Cisplatin exposure enhances the PMS2–p73 association, and PMS2 is required for cisplatin-stimulated p73-dependent apoptosis. Co-immunoprecipitation, subcellular fractionation, cisplatin cytotoxicity assays in PMS2-deficient vs. reconstituted cells Proceedings of the National Academy of Sciences of the United States of America Medium 12601175
2003 Nuclear import of MutLα (MLH1–PMS2 heterodimer) depends on C-terminal dimerization of the two subunits. Although both proteins possess functional nuclear localization signals (NLS) and nuclear export sequences individually, dimerization unmasks the NLS and is required for efficient nuclear import. Nuclear fractionation, NLS mutagenesis, transfection of individual vs. co-expressed MLH1/PMS2 in mismatch-repair-deficient cells Molecular and cellular biology Medium 12697830
2005 The C-terminal homology (CTH) domain of MLH1 is essential for stabilizing PMS2 steady-state levels and for forming stable MutLα heterodimers. Truncation of the CTH (MLH1-L749X or MLH1-Y750X) prevents intracellular stabilization of PMS2, abrogates spontaneous mutation suppression, and eliminates cytotoxic response to 6-thioguanine. Transfection of CTH-truncated MLH1 into MLH1-deficient and Mlh1-/-;Pms2-/- fibroblasts; co-immunoprecipitation; clonogenic survival; spontaneous mutation assays DNA repair High 16338176
2009 Human PMS2 contains a single monopartite NLS in its linker region. Although MutLα can be imported via the NLS of either MLH1 (bipartite) or PMS2 (monopartite), the MLH1 NLS drives import of the heterodimer even when the PMS2 NLS is mutated, providing redundancy that ensures nuclear localization. Confocal microscopy of transfected fluorescent-tagged proteins; NLS mutagenesis; nuclear import assays in mismatch-repair-deficient cells Molecular carcinogenesis Medium 19148896
2017 Crystal structures of importin-α bound to NLS peptides of MLH1 and PMS2 show both bind as monopartite NLSs. MLH1-NLS has higher affinity for importin-α than PMS2-NLS, indicating MLH1 plays the dominant role in nuclear import of the MutLα heterodimer. X-ray crystallography of importin-α/NLS peptide complexes; isothermal titration calorimetry Biochimie High 29175432
2010 The PMS2 endonuclease activity (mapped to E702, requiring the intact DQHA(X)2E(X)4E motif) is essential for genome maintenance, tumor suppression, and class switch recombination but is dispensable for somatic hypermutation and for spermatogenesis. Endonuclease-dead Pms2E702K knock-in mice show elevated mutation rates and strong cancer predisposition. Generation of endonuclease-dead Pms2E702K knock-in mice; in vivo mutation rate assays; B-cell class switch recombination and somatic hypermutation assays; tumor incidence monitoring; male fertility assessment Proceedings of the National Academy of Sciences of the United States of America High 20624957
2017 Human PCNA interacts specifically with the C-terminal endonuclease domain of the PMS2 subunit of MutLα via a 721QRLIAP motif. Amino acid substitutions in this PMS2 motif abolish PCNA interaction, PCNA-dependent activation of MutLα endonuclease, PCNA- and DNA-dependent MutLα ATPase activation, and MutLα function in in vitro mismatch repair. The corresponding yeast PMS1 motif is functionally equivalent in vivo. In vitro protein interaction assays; site-directed mutagenesis of PMS2 PCNA-interaction motif; in vitro mismatch repair reconstitution; endonuclease activity assays; yeast genetic epistasis Proceedings of the National Academy of Sciences of the United States of America High 28439008
1995 PMS2 is required for DNA mismatch repair in vivo: Pms2-null mice display microsatellite instability in germline and somatic tissues, develop sarcomas and lymphomas, and males are infertile with abnormal spermatogenesis and defects in meiotic chromosome synapsis. Gene targeting/knockout in embryonic stem cells; microsatellite instability analysis; histological examination of spermatogenesis and synaptonemal complex formation Cell High 7628019
1997 Pms2-null mice show a ~100-fold elevation in spontaneous mutation frequency across multiple tissues, with mutations predominantly consisting of 1-bp deletions and insertions at mononucleotide repeat sequences, consistent with PMS2 correcting DNA replication slippage errors. Lambda phage shuttle vector mutation reporter assay in Pms2-/- transgenic mice; sequence analysis of recovered mutants Proceedings of the National Academy of Sciences of the United States of America High 9096356
1999 Pms2-null mice retain near-normal Mlh1 protein levels, whereas Mlh1-null mice lose both Mlh1 and Pms2. Mlh1-null animals have 2–3-fold higher mononucleotide repeat mutation frequencies than Pms2-null animals. Mlh1-/-;Pms2-/- double knockouts show no additional mutator phenotype beyond Mlh1 single knockouts, indicating Mlh1 nullizygosity is sufficient to fully inactivate MMR and that the more severe phenotype of Mlh1-/- mice reflects combined loss of both proteins. Single-molecule PCR and in vivo forward mutation assays at microsatellite loci in knockout mouse strains; protein expression by Western blot Proceedings of the National Academy of Sciences of the United States of America High 10359802
2005 MLH3 and PMS2 have partially overlapping roles in mismatch repair and tumor suppression. Mlh3-/-;Pms2-/- double-knockout mice phenocopy Mlh1-/- mice in tumor susceptibility, lifespan, microsatellite instability, and DNA-damage response, whereas single knockouts have milder phenotypes, demonstrating functional redundancy between MLH1/MLH3 and MLH1/PMS2 complexes. Generation of Mlh3-/-;Pms2-/- double-knockout mice; tumor incidence monitoring; microsatellite instability assays; DNA-damage response assays; comparison to Mlh1-/- single knockouts Cancer research High 16204034
1998 PMS2-deficient mice show altered somatic hypermutation spectra in immunoglobulin variable genes: significantly more adjacent (tandem) base substitutions compared to wild-type. A biochemical assay confirmed that PMS2-proficient cells repair tandem mispairs whereas Pms2-/- cells do not, defining a PMS2-dependent pathway for processing tandem substitutions generated during hypermutation. Ig variable gene sequencing in Pms2-/- mice; biochemical tandem mispair repair assay comparing wild-type vs. Pms2-/- cells Proceedings of the National Academy of Sciences of the United States of America High 9618520
2000 Pms2 deficiency and p53 deficiency reduce ionizing radiation (IR)-induced apoptosis via separate, non-overlapping pathways. Double-null (Pms2-/-;p53-/-) cells show additive reduction in IR-induced apoptosis and increased clonogenic survival, demonstrating that PMS2-mediated IR apoptosis is p53-independent. Apoptosis assays and clonogenic survival after ionizing radiation in primary fibroblasts from Pms2-/-, p53-/-, and double-null mice Cancer research High 10987303
1997 Loss of MMR via PMS2 knockout confers resistance to the platinum compounds cisplatin and carboplatin (~1.9-fold and ~1.5-fold, respectively) in isogenic cell lines, demonstrating PMS2 is required for the pro-apoptotic signaling triggered by platinum adducts. Clonogenic survival assays comparing isogenic Pms2-/- vs. Pms2+/+ mouse fibroblasts after cisplatin/carboplatin treatment International journal of oncology Medium 21528244
2008 The PMS2 R20Q polymorphic variant is defective in activating p73-dependent apoptosis in response to cisplatin. When expressed in Pms2-/- mouse fibroblasts, PMS2(R20Q) fails to restore cisplatin-induced p73 activation and does not enhance cisplatin cytotoxicity, unlike wild-type PMS2. Transfection of PMS2(R20Q) vs. wild-type PMS2 into Pms2-/- fibroblasts; apoptosis assays; clonogenic survival; p73 activation measurement Proceedings of the National Academy of Sciences of the United States of America Medium 18768816
2005 PMS2 and MLH1 are direct transcriptional targets of p53: both genes contain p53 response elements within their first intron and are upregulated in response to DNA damage and p53 activation in normal human fibroblasts. Serial analysis of binding elements (SABE) chromatin immunoprecipitation; reporter assays for p53-response element activity; gene expression analysis after DNA damage in normal fibroblasts Proceedings of the National Academy of Sciences of the United States of America Medium 15781865
2006 Overexpression of human PMS2 in mouse fibroblasts causes hypermutability (elevated spontaneous and MNU-induced mutation frequencies) and DNA damage tolerance (increased survival after MNU), consistent with PMS2 overabundance disrupting the stoichiometry of the MMR complex. A truncating PMS2 variant (R134X) causes the same phenotype. Transfection of hPMS2 expression vector into mouse fibroblasts; lambda phage reporter gene mutation assays; clonogenic survival assays after MNU Cancer letters Medium 16426742
2002 Three PMS2 missense variants previously classified as polymorphisms (P511K, T597S, M622I) cause defective PMS2–MLH1 protein–protein interaction in a functional assay, identifying an interaction domain outside the previously known binding region. Yeast two-hybrid and/or co-expression interaction assays testing PMS2 polymorphic variants for MLH1 binding Human mutation Medium 11793469
2012 Pms2 specifically suppresses large GAA·TTC repeat expansions in neuronal tissues (cerebellum, cerebrum, dorsal root ganglia) but not in non-neuronal tissues, and acts in tissues showing MutSα-dependent instability, suggesting Pms2 may antagonize the MutSα-initiated expansion pathway in post-mitotic neurons. Analysis of somatic instability of expanded (GAA·TTC)n sequence in Pms2-/- transgenic mice carrying human FXN locus; comparison across tissues by PCR-based size analysis PloS one Medium 23071719
2020 PMS2 endonuclease activity promotes homologous recombination (HR) in non-meiotic somatic cells. PMS2-/- and endonuclease-dead PMS2EK/EK human B cells show ~2.5-fold decreased heteroallelic HR repair of restriction enzyme-induced DSBs, delayed resolution of Rad51 foci, and reduced cisplatin-induced sister chromatid exchanges. The effect of PMS2EK/EK and MLH3DN/DN mutations is additive, and ectopic Gen1 HJ resolvase partially rescues HR defects. Gene disruption and knock-in of endonuclease-dead mutations in human TK6 cells; heteroallelic HR assay; γ-H2AX/Rad51 foci kinetics; sister chromatid exchange assays; Gen1 rescue experiment The Journal of biological chemistry High 33453991
2017 During somatic hypermutation, Pms2/Mlh1 (the nicking complex) and uracil-DNA glycosylases (UNG, TDG, SMUG1) act jointly but with distinct strand biases to generate mutations at A-T base pairs. Ung-deficient mice show a 50% reduction in A-T mutations, and the remaining A-T mutations largely depend on TDG and SMUG1, demonstrating that uracil glycosylases provide the nick required for PMS2/MLH1-dependent error-prone synthesis. Immunoglobulin gene mutation spectrum analysis in Ung-/-;Pms2 compound-deficient mice and triple-glycosylase mutant mice; cell-cycle staging of mutagenesis The Journal of experimental medicine Medium 28283534
2010 GSK-3β physically interacts with PMS2 and stabilizes PMS2 protein levels in HeLa cells. siRNA knockdown of GSK-3β reduces PMS2 expression, and overexpression of PMS2 enhances HeLa cell sensitivity to cisplatin. Co-immunoprecipitation; GSK-3β siRNA knockdown; PMS2 transfection; cisplatin cytotoxicity assays BMC cancer Low 20178594
2003 Mlh1- and Pms2-dependent apoptosis in the mouse small intestine is induced by temozolomide (100 mg/kg) and low-dose NMNU (10 mg/kg) but not by high-dose NMNU (50 mg/kg). When MutLα-dependent apoptosis is impaired, mutation frequency in intestinal cells increases, directly linking MutLα apoptotic function to in vivo mutation avoidance. In vivo apoptosis assays and in vivo mutation frequency measurements in Mlh1-/- and Pms2-/- mice after alkylating agent treatment at different doses DNA repair Medium 12967659
2016 Deoxyinosine triphosphate (dITP)-induced cell growth arrest and DNA instability in mammalian cells depend on MLH1/PMS2 and p53. ITPA-deficient cells accumulate nuclear single-strand breaks and show elevated p53/p21 levels in an MLH1-dependent manner; MSH2 and other repair proteins are not required for this response. Analysis of ITPA-deficient human and mouse cells; MLH1/PMS2 knockdown; p53/p21 expression assays; single-strand break quantification Scientific reports Medium 27618981

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell 466 7628019
2008 The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology 423 18602922
1998 Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DNA mismatch repair. Nature genetics 311 9500552
2011 Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomas. International journal of cancer 254 21425258
2004 Microsatellite instability, immunohistochemistry, and additional PMS2 staining in suspected hereditary nonpolyposis colorectal cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 182 14871975
2014 Lynch syndrome caused by germline PMS2 mutations: delineating the cancer risk. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 172 25512458
2018 Cancer Risks for PMS2-Associated Lynch Syndrome. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 165 30161022
2004 Novel PMS2 pseudogenes can conceal recessive mutations causing a distinctive childhood cancer syndrome. American journal of human genetics 148 15077197
2005 Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer. Gastroenterology 140 15887099
1997 Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2. Proceedings of the National Academy of Sciences of the United States of America 138 9096356
2018 MSH6 and PMS2 germ-line pathogenic variants implicated in Lynch syndrome are associated with breast cancer. Genetics in medicine : official journal of the American College of Medical Genetics 133 29345684
2020 Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors. International journal of cancer 130 32449172
2004 Mismatch repair gene PMS2: disease-causing germline mutations are frequent in patients whose tumors stain negative for PMS2 protein, but paralogous genes obscure mutation detection and interpretation. Cancer research 127 15256438
1999 Different mutator phenotypes in Mlh1- versus Pms2-deficient mice. Proceedings of the National Academy of Sciences of the United States of America 121 10359802
2003 Interaction of mismatch repair protein PMS2 and the p53-related transcription factor p73 in apoptosis response to cisplatin. Proceedings of the National Academy of Sciences of the United States of America 120 12601175
2006 Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome). Gastroenterology 110 16472587
2010 Immunohistochemistry for PMS2 and MSH6 alone can replace a four antibody panel for mismatch repair deficiency screening in colorectal adenocarcinoma. Pathology 109 20632815
2001 Structure and function of the N-terminal 40 kDa fragment of human PMS2: a monomeric GHL ATPase. The EMBO journal 100 11574484
1995 Genomic organization of the human PMS2 gene family. Genomics 100 8586419
2005 Identification of the mismatch repair genes PMS2 and MLH1 as p53 target genes by using serial analysis of binding elements. Proceedings of the National Academy of Sciences of the United States of America 88 15781865
2006 Long-range PCR facilitates the identification of PMS2-specific mutations. Human mutation 87 16619239
1998 Altered spectra of hypermutation in antibodies from mice deficient for the DNA mismatch repair protein PMS2. Proceedings of the National Academy of Sciences of the United States of America 86 9618520
2010 Clinical analysis of PMS2: mutation detection and avoidance of pseudogenes. Human mutation 84 20205264
2005 Contributions by MutL homologues Mlh3 and Pms2 to DNA mismatch repair and tumor suppression in the mouse. Cancer research 83 16204034
2003 Dimerization of MLH1 and PMS2 limits nuclear localization of MutLalpha. Molecular and cellular biology 65 12697830
2006 PMS2 mutations in childhood cancer. Journal of the National Cancer Institute 64 16507833
2013 Reduction of MLH1 and PMS2 confers temozolomide resistance and is associated with recurrence of glioblastoma. Oncotarget 62 24259277
2008 RNA-based mutation analysis identifies an unusual MSH6 splicing defect and circumvents PMS2 pseudogene interference. Human mutation 61 18030674
2019 NTRK gene rearrangements are highly enriched in MLH1/PMS2 deficient, BRAF wild-type colorectal carcinomas-a study of 4569 cases. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 57 31792356
2010 Quantification of sequence exchange events between PMS2 and PMS2CL provides a basis for improved mutation scanning of Lynch syndrome patients. Human mutation 57 20186688
2010 PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance. Proceedings of the National Academy of Sciences of the United States of America 57 20624957
2007 Novel biallelic mutations in MSH6 and PMS2 genes: gene conversion as a likely cause of PMS2 gene inactivation. Human mutation 57 17557300
2011 Paediatric intestinal cancer and polyposis due to bi-allelic PMS2 mutations: case series, review and follow-up guidelines. European journal of cancer (Oxford, England : 1990) 55 21376568
2002 Contribution of human mlh1 and pms2 ATPase activities to DNA mismatch repair. The Journal of biological chemistry 55 11897781
2016 Up-regulation of mismatch repair genes MSH6, PMS2 and MLH1 parallels development of genetic instability and is linked to tumor aggressiveness and early PSA recurrence in prostate cancer. Carcinogenesis 54 27803051
2016 Isolated Loss of PMS2 Immunohistochemical Expression is Frequently Caused by Heterogenous MLH1 Promoter Hypermethylation in Lynch Syndrome Screening for Endometrial Cancer Patients. The American journal of surgical pathology 52 26848797
2016 Comprehensive Mutation Analysis of PMS2 in a Large Cohort of Probands Suspected of Lynch Syndrome or Constitutional Mismatch Repair Deficiency Syndrome. Human mutation 52 27435373
2015 Germline MLH1 Mutations Are Frequently Identified in Lynch Syndrome Patients With Colorectal and Endometrial Carcinoma Demonstrating Isolated Loss of PMS2 Immunohistochemical Expression. The American journal of surgical pathology 52 25871621
2015 PMS2 monoallelic mutation carriers: the known unknown. Genetics in medicine : official journal of the American College of Medical Genetics 51 25856668
2017 Interaction of proliferating cell nuclear antigen with PMS2 is required for MutLα activation and function in mismatch repair. Proceedings of the National Academy of Sciences of the United States of America 50 28439008
2013 Refining the role of PMS2 in Lynch syndrome: germline mutational analysis improved by comprehensive assessment of variants. Journal of medical genetics 49 23709753
2012 Pms2 suppresses large expansions of the (GAA·TTC)n sequence in neuronal tissues. PloS one 49 23071719
2007 Extensive gene conversion at the PMS2 DNA mismatch repair locus. Human mutation 49 17253626
2005 Isolated loss of PMS2 expression in colorectal cancers: frequency, patient age, and familial aggregation. Clinical cancer research : an official journal of the American Association for Cancer Research 46 16166421
2015 Relationship between MLH-1, MSH-2, PMS-2,MSH-6 expression and clinicopathological features in colorectal cancer. International journal of clinical and experimental pathology 44 26097592
2008 A frame-shift mutation of PMS2 is a widespread cause of Lynch syndrome. Journal of medical genetics 44 18178629
2000 Ionizing radiation-induced apoptosis via separate Pms2- and p53-dependent pathways. Cancer research 44 10987303
2015 Abrupt loss of MLH1 and PMS2 expression in endometrial carcinoma: molecular and morphologic analysis of 6 cases. The American journal of surgical pathology 43 25786082
2000 Mutagenesis in PMS2- and MSH2-deficient mice indicates differential protection from transversions and frameshifts. Carcinogenesis 43 10874005
2005 Truncation of the C-terminus of human MLH1 blocks intracellular stabilization of PMS2 and disrupts DNA mismatch repair. DNA repair 42 16338176
2007 Genetic investigation of DNA-repair pathway genes PMS2, MLH1, MSH2, MSH6, MUTYH, OGG1 and MTH1 in sporadic colon cancer. International journal of cancer 39 17417778
1998 Enhanced intestinal adenomatous polyp formation in Pms2-/-;Min mice. Cancer research 39 9515784
1995 Analysis of the 5' region of PMS2 reveals heterogeneous transcripts and a novel overlapping gene. Genomics 39 8666379
2003 Alterations in PMS2, MSH2 and MLH1 expression in human prostate cancer. International journal of oncology 38 12684669
2006 Overexpression of the DNA mismatch repair factor, PMS2, confers hypermutability and DNA damage tolerance. Cancer letters 37 16426742
2006 Homozygous PMS2 deletion causes a severe colorectal cancer and multiple adenoma phenotype without extraintestinal cancer. Gastroenterology 37 17258725
2016 Germline mutations in PMS2 and MLH1 in individuals with solitary loss of PMS2 expression in colorectal carcinomas from the Colon Cancer Family Registry Cohort. BMJ open 36 26895986
2015 A Comprehensive Strategy for Accurate Mutation Detection of the Highly Homologous PMS2. The Journal of molecular diagnostics : JMD 36 26320870
2010 MSH6 and PMS2 mutation positive Australian Lynch syndrome families: novel mutations, cancer risk and age of diagnosis of colorectal cancer. Hereditary cancer in clinical practice 36 20487569
2007 Elevated levels of the mismatch repair protein PMS2 are associated with prostate cancer. The Prostate 35 17044039
2011 Avoidance of pseudogene interference in the detection of 3' deletions in PMS2. Human mutation 33 21618646
2018 The changing landscape of Lynch syndrome due to PMS2 mutations. Clinical genetics 31 29286535
2015 A homozygous PMS2 founder mutation with an attenuated constitutional mismatch repair deficiency phenotype. Journal of medical genetics 31 25691505
2014 Promoter methylation of MLH1, PMS2, MSH2 and p16 is a phenomenon of advanced-stage HCCs. PloS one 31 24400091
2009 PMS2 involvement in patients suspected of Lynch syndrome. Genes, chromosomes & cancer 31 19132747
1999 Mice defective in the DNA mismatch gene PMS2 are hypersensitive to MNU induced thymic lymphoma and are partially protected by transgenic expression of human MGMT. Oncogene 31 10439048
2001 Hypermutability to ionizing radiation in mismatch repair-deficient, Pms2 knockout mice. Cancer research 28 11325851
2008 Examination of chromosome 7p22 candidate genes RBaK, PMS2 and GNA12 in familial hyperaldosteronism type II. Clinical and experimental pharmacology & physiology 27 18307725
1998 Lack of PMS2 gene-truncating mutations in patients with hereditary colorectal cancer. International journal of oncology 27 9683794
2013 Inactivation of DNA mismatch repair by variants of uncertain significance in the PMS2 gene. Human mutation 26 24027009
1997 Loss of DNA mismatch repair due to knockout of MSH2 or PMS2 results in resistance to cisplatin and carboplatin. International journal of oncology 26 21528244
2019 PMS2 expression decrease causes severe problems in mismatch repair. Human mutation 24 30946512
2017 Homozygous germ-line mutation of the PMS2 mismatch repair gene: a unique case report of constitutional mismatch repair deficiency (CMMRD). BMC medical genetics 24 28381238
2006 The added value of PMS2 immunostaining in the diagnosis of hereditary nonpolyposis colorectal cancer. Familial cancer 24 16817031
2002 Polymorphisms and HNPCC: PMS2-MLH1 protein interactions diminished by single nucleotide polymorphisms. Human mutation 24 11793469
2018 Detecting clinically actionable variants in the 3' exons of PMS2 via a reflex workflow based on equivalent hybrid capture of the gene and its pseudogene. BMC medical genetics 23 30268105
2012 The frequency of previously undetectable deletions involving 3' Exons of the PMS2 gene. Genes, chromosomes & cancer 23 23012243
2020 Genetic evidence for the involvement of mismatch repair proteins, PMS2 and MLH3, in a late step of homologous recombination. The Journal of biological chemistry 22 33453991
2018 Colorectal Carcinomas With Isolated Loss of PMS2 Staining by Immunohistochemistry. Archives of pathology & laboratory medicine 22 29336605
2009 Nuclear import of human MLH1, PMS2, and MutLalpha: redundancy is the key. Molecular carcinogenesis 22 19148896
2022 Concurrent loss of MLH1, PMS2 and MSH6 immunoexpression in digestive system cancers indicating a widespread dysregulation in DNA repair processes. Frontiers in oncology 21 36387226
2023 PMS2-associated Lynch syndrome: Past, present and future. Frontiers in oncology 19 36895471
2019 Immunohistochemical expression of mismatch repair proteins (MSH2, MSH6, MLH1, and PMS2) in prostate cancer: correlation with grade groups (WHO 2016) and ERG and PTEN status. Virchows Archiv : an international journal of pathology 19 31209634
2017 Pms2 and uracil-DNA glycosylases act jointly in the mismatch repair pathway to generate Ig gene mutations at A-T base pairs. The Journal of experimental medicine 19 28283534
2015 The effect of genotypes and parent of origin on cancer risk and age of cancer development in PMS2 mutation carriers. Genetics in medicine : official journal of the American College of Medical Genetics 18 26110232
2012 Recurrent and founder mutations in the PMS2 gene. Clinical genetics 18 22577899
2002 Loss of heterozygosity and point mutation at Aprt locus in T cells and fibroblasts of Pms2-/- mice. Oncogene 18 11973643
1999 Transgenic expression of human MGMT blocks the hypersensitivity of PMS2-deficient mice to low dose MNU thymic lymphomagenesis. Carcinogenesis 18 10469609
2020 Prevalence of CNV-neutral structural genomic rearrangements in MLH1, MSH2, and PMS2 not detectable in routine NGS diagnostics. Familial cancer 17 32002723
2010 Deficient Pms2, ERCC1, Ku86, CcOI in field defects during progression to colon cancer. Journal of visualized experiments : JoVE 17 20689513
2008 Apoptotic function of human PMS2 compromised by the nonsynonymous single-nucleotide polymorphic variant R20Q. Proceedings of the National Academy of Sciences of the United States of America 17 18768816
2003 Apoptosis and mutation in the murine small intestine: loss of Mlh1- and Pms2-dependent apoptosis leads to increased mutation in vivo. DNA repair 17 12967659
2022 Collision of germline POLE and PMS2 variants in a young patient treated with immune checkpoint inhibitors. NPJ precision oncology 16 35260767
2019 The complexity of screening PMS2 in DNA isolated from formalin-fixed paraffin-embedded material. European journal of human genetics : EJHG 16 31616036
2010 Stabilization of mismatch repair gene PMS2 by glycogen synthase kinase 3beta is implicated in the treatment of cervical carcinoma. BMC cancer 16 20178594
2021 The coding microsatellite mutation profile of PMS2-deficient colorectal cancer. Experimental and molecular pathology 15 34302852
2020 Helicobacter pylori severely reduces expression of DNA repair proteins PMS2 and ERCC1 in gastritis and gastric cancer. DNA repair 15 32143126
2017 DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway. Biochimie 15 29175432
2016 Deoxyinosine triphosphate induces MLH1/PMS2- and p53-dependent cell growth arrest and DNA instability in mammalian cells. Scientific reports 15 27618981
2009 Epitope-positive truncating MLH1 mutation and loss of PMS2: implications for IHC-directed genetic testing for Lynch syndrome. Familial cancer 15 19672700

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