MLH3

Summary

Gene Symbol: MLH3
Description: mutL homolog 3
Alias: HNPCC7, DNA mismatch repair protein Mlh3
Species: human
Products:     MLH3

Top Publications

  1. Cannavo E, Marra G, Sabates Bellver J, Menigatti M, Lipkin S, Fischer F, et al. Expression of the MutL homologue hMLH3 in human cells and its role in DNA mismatch repair. Cancer Res. 2005;65:10759-66 pubmed
    ..Sterility of Mlh1-/-, Pms2-/-, and Mlh3-/- mice implicated the Mlh1/Pms2 and Mlh1/Mlh3 heterodimers in meiotic recombination...
  2. Chen P, Kuraguchi M, Velasquez J, Wang Y, Yang K, Edwards R, et al. Novel roles for MLH3 deficiency and TLE6-like amplification in DNA mismatch repair-deficient gastrointestinal tumorigenesis and progression. PLoS Genet. 2008;4:e1000092 pubmed publisher
    ..Four mammalian E. coli MutL homologues heterodimerize to form three distinct complexes: MLH1/PMS2, MLH1/MLH3, and MLH1/PMS1...
  3. Liu H, Li Y, Jiang X, Yin H, Zhang L, Wang Y, et al. Mutation screening of mismatch repair gene Mlh3 in familial esophageal cancer. World J Gastroenterol. 2006;12:5281-6 pubmed
    To shed light on the possible role of mismatch repair gene Mlh3 in familial esophageal cancer (FEC)...
  4. Lipkin S, Wang V, Jacoby R, Banerjee Basu S, Baxevanis A, Lynch H, et al. MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability. Nat Genet. 2000;24:27-35 pubmed
    ..Here we describe the cloning and complete genomic sequence of MLH3, which encodes a new DNA mismatch repair protein that interacts with MLH1...
  5. Charbonneau N, Amunugama R, Schmutte C, Yoder K, Fishel R. Evidence that hMLH3 functions primarily in meiosis and in hMSH2-hMSH3 mismatch repair. Cancer Biol Ther. 2009;8:1411-20 pubmed
    ..These data are consistent with yeast studies and suggest a role for hMLH3 in meiosis as well as hMSH2-hMSH3 repair processes and little if any role in Hereditary Non-Polyposis Colorectal Cancer (HNPCC). ..
  6. Ou J, Rasmussen M, Westers H, Andersen S, Jager P, Kooi K, et al. Biochemical characterization of MLH3 missense mutations does not reveal an apparent role of MLH3 in Lynch syndrome. Genes Chromosomes Cancer. 2009;48:340-50 pubmed publisher
    So far 18 MLH3 germline mutations/variants have been identified in familial colorectal cancer cases. Sixteen of these variants are amino acid substitutions of which the pathogenic nature is still unclear...
  7. Hienonen T, Laiho P, Salovaara R, Mecklin J, Jarvinen H, Sistonen P, et al. Little evidence for involvement of MLH3 in colorectal cancer predisposition. Int J Cancer. 2003;106:292-6 pubmed
    ..The role of a relatively recently cloned MMR gene, MLH3, in familial CRC has been studied; but the results appear somewhat conflicting...
  8. Korhonen M, Vuorenmaa E, Nyström M. The first functional study of MLH3 mutations found in cancer patients. Genes Chromosomes Cancer. 2008;47:803-9 pubmed publisher
    The MLH3 gene is one of the five mismatch repair (MMR) genes associated with hereditary nonpolyposis colorectal cancer (HNPCC)...
  9. de Jong M, Hofstra R, Kooi K, Westra J, Berends M, Wu Y, et al. No association between two MLH3 variants (S845G and P844L)and colorectal cancer risk. Cancer Genet Cytogenet. 2004;152:70-1 pubmed
    Recently we identified a new variant, S845G, in the MLH3 gene in 7 out of 327 patients suspected of hereditary nonpolyposis colorectal cancer but not fulfilling the Amsterdam criteria and in 1 out of 188 control subjects...

More Information

Publications77

  1. Taylor N, Powell M, Gibb R, Rader J, Huettner P, Thibodeau S, et al. MLH3 mutation in endometrial cancer. Cancer Res. 2006;66:7502-8 pubmed
    b>MLH3 is a recently described member of the DNA mismatch repair gene family. Based on its interaction with the MutL homologue MLH1, it was postulated that MLH3 might play a role in tumorigenesis...
  2. Milano C, Holloway J, Zhang Y, Jin B, Smith C, Bergman A, et al. Mutation of the ATPase Domain of MutS Homolog-5 (MSH5) Reveals a Requirement for a Functional MutSγ Complex for All Crossovers in Mammalian Meiosis. G3 (Bethesda). 2019;: pubmed publisher
    ..only 10% of DSBs resolve as COs, mostly through a class I pathway dependent on MutSg (MSH4/ MSH5) and MutLg (MLH1/MLH3), the latter representing the ultimate marker of these CO events...
  3. Valle L, de Voer R, Goldberg Y, Sjursen W, Forsti A, Ruiz Ponte C, et al. Update on genetic predisposition to colorectal cancer and polyposis. Mol Aspects Med. 2019;: pubmed publisher
    ..polyposis, mismatch repair gene biallelic inactivation-related adenomatous polyposis (including MSH3- and MLH3-associated polyposes), GREM1-associated mixed polyposis, RNF43-associated serrated polyposis, and RPS20 mutations ..
  4. Zhao X, Zhang Y, Wilkins K, Edelmann W, Usdin K. MutLγ promotes repeat expansion in a Fragile X mouse model while EXO1 is protective. PLoS Genet. 2018;14:e1007719 pubmed publisher
    ..Here we show that MLH1/MLH3 (MutLγ), a protein complex that can act downstream of MutSβ in MMR, is also required for all germ line and ..
  5. Roncati L. Microsatellite Instability Predicts Response to Anti-PD1 Immunotherapy in Metastatic Melanoma. Acta Dermatovenerol Croat. 2018;26:341-343 pubmed
    ..In humans, seven DNA MMR proteins (Mlh1, Mlh3, Msh2, Msh3, Msh6, Pms1, and Pms2) work in a coordinated and sequential manner to repair DNA mismatches...
  6. Olkinuora A, Nieminen T, Mårtensson E, Rohlin A, Ristimaki A, Koskenvuo L, et al. Biallelic germline nonsense variant of MLH3 underlies polyposis predisposition. Genet Med. 2018;: pubmed publisher
    ..The DNA mismatch repair (MMR) gene MLH3 (MutL Homolog 3) was pinpointed and prompted a subsequent screen of ~1000 Swedish patients referred to clinical ..
  7. De Angelis G, Bottarelli L, Azzoni C, De Angelis N, Leandro G, Di Mario F, et al. Microsatellite instability in colorectal cancer. Acta Biomed. 2018;89:97-101 pubmed publisher
    ..Proteins within the MMR system include MLH1, PMS2, MSH2, MSH6, MLH3, MSH3, PMS1, and Exo1...
  8. Roesner L, Mielke C, Faehnrich S, Merkhoffer Y, Dittmar K, Drexler H, et al. Localization of MLH3 at the centrosomes. Int J Mol Sci. 2014;15:13932-7 pubmed publisher
    ..MLH1 protein heterodimerizes with PMS2, PMS1, and MLH3 to form MutLα, MutLβ, and MutLγ, respectively...
  9. Beggs A, Domingo E, Abulafi M, Hodgson S, Tomlinson I. A study of genomic instability in early preneoplastic colonic lesions. Oncogene. 2013;32:5333-7 pubmed publisher
    ..Significant promoter methylation was seen in MLH1, PMS2, MLH3 and MSH3 as well as significant heterogeneity for both MSI and promoter methylation...
  10. Muro Y, Sugiura K, Mimori T, Akiyama M. DNA mismatch repair enzymes: genetic defects and autoimmunity. Clin Chim Acta. 2015;442:102-9 pubmed publisher
    ..The human MutS enzymes consist of MSH2, MSH3 and MSH6, and the human MutL enzymes include MLH1, MLH3, PMS1 and PMS2...
  11. Carta C, Oliveira Alves M, de Barros P, Campos M, Scholz J, Jorge A, et al. Screening methylation of DNA repair genes in the oral mucosa of chronic smokers. Arch Oral Biol. 2018;92:83-87 pubmed publisher
    ..Highest percentages of methylation were observed for MLH3 and XRCC1 genes (11-20% methylation) and in one case for MRE11A and PMS2 (>50% methylation)...
  12. Anifandis G, Markandona O, Dafopoulos K, Messini C, Tsezou A, Dimitraki M, et al. Embryological Results of Couples Undergoing ICSI-ET Treatments with Males Carrying the Single Nucleotide Polymorphism rs175080 of the MLH3 Gene. Int J Mol Sci. 2017;18: pubmed publisher
    Human MLH3 (hMLH3) gene has been suggested to play a role in the DNA mismatch repair mechanism, while it may also be associated with abnormal spermatogenesis and subsequently male infertility...
  13. Yang J, Wang X, Zou S, Li H, Xiao Q, Feng Y, et al. [Genetic variations in MLH3 and MSH2 genes are associated with the sensitivity and prognosis in locally advanced rectal cancer patients receiving preoperative chemoradiotherapy]. Zhonghua Zhong Liu Za Zhi. 2018;40:433-440 pubmed publisher
    ..b>Methods: Fourteen haplotype-tagging single nucleotide polymorphisms (htSNPs) of MLH1, MLH3 and MSH2 genes were genotyped by Sequenom MassARRAY method in 146 patients with locally advanced rectal cancer who ..
  14. Kunstman J, Juhlin C, Goh G, Brown T, Stenman A, Healy J, et al. Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing. Hum Mol Genet. 2015;24:2318-29 pubmed publisher
    ..to malignancy not previously associated with thyroid tumorigenesis were observed, including mTOR, NF1, NF2, MLH1, MLH3, MSH5, MSH6, ERBB2, EIF1AX and USH2A; some of which were recurrent and were investigated in 24 additional ATC cases ..
  15. Muro Y, Nakashima R, Hosono Y, Sugiura K, Mimori T, Akiyama M. Autoantibodies to DNA mismatch repair enzymes in polymyositis/dermatomyositis and other autoimmune diseases: a possible marker of favorable prognosis. Arthritis Rheumatol. 2014;66:3457-62 pubmed
    ..was undertaken to determine the frequencies and clinical associations of antibodies to 7 types of MMREs (MLH1, MLH3, MSH2,MSH3, MSH6, PMS1, and PMS2) in patients with IIMs and other systemic autoimmune diseases.Methods...
  16. Kucherlapati M. Examining transcriptional changes to DNA replication and repair factors over uveal melanoma subtypes. BMC Cancer. 2018;18:818 pubmed publisher
    ..alteration include MCM2, MCM4, MCM5, CDC45, MCM10, CIZ1, PCNA, FEN1, LIG1, POLD1, POLE, HUS1, CHECK1, ATRIP, MLH3, and MSH6...
  17. Bady P, Kurscheid S, Delorenzi M, Gorlia T, van den Bent M, Hoang Xuan K, et al. The DNA methylome of DDR genes and benefit from RT or TMZ in IDH mutant low-grade glioma treated in EORTC 22033. Acta Neuropathol. 2018;135:601-615 pubmed publisher
    ..seven CpGs of four DDR genes may be predictive for longer PFS in one of the treatment arms that comprised MGMT, MLH3, RAD21, and SMC4...
  18. Gallardo I, Pasupathy P, Brown M, Manhart C, Neikirk D, Alani E, et al. High-Throughput Universal DNA Curtain Arrays for Single-Molecule Fluorescence Imaging. Langmuir. 2015;31:10310-7 pubmed publisher
    ..As a first proof of principle, we track the diffusion of Mlh1-Mlh3-a heterodimeric complex that participates in DNA mismatch repair and meiotic recombination...
  19. Manhart C, Alani E. Roles for mismatch repair family proteins in promoting meiotic crossing over. DNA Repair (Amst). 2016;38:84-93 pubmed publisher
    The mismatch repair (MMR) family complexes Msh4-Msh5 and Mlh1-Mlh3 act with Exo1 and Sgs1-Top3-Rmi1 in a meiotic double strand break repair pathway that results in the asymmetric cleavage of double Holliday junctions (dHJ) to form ..
  20. Zhao C, Li S, Zhao M, Zhu H, Zhu X. Prognostic values of DNA mismatch repair genes in ovarian cancer patients treated with platinum-based chemotherapy. Arch Gynecol Obstet. 2018;297:153-159 pubmed publisher
    ..In the current study, we systemically investigated the prognostic roles of seven MMR genes, MSH2, MSH3, MSH6, MLH1, MLH3, PMS1 and PMS2, in ovarian cancer patients treated with platinum-based chemotherapy through "The Kaplan-Meier ..
  21. Claeys Bouuaert C, Keeney S. Distinct DNA-binding surfaces in the ATPase and linker domains of MutL? determine its substrate specificities and exert separable functions in meiotic recombination and mismatch repair. PLoS Genet. 2017;13:e1006722 pubmed publisher
    Mlh1-Mlh3 (MutL?) is a mismatch repair factor with a central role in formation of meiotic crossovers, presumably through resolution of double Holliday junctions...
  22. Voelkel Meiman K, Johnston C, Thappeta Y, Subramanian V, Hochwagen A, MacQueen A. Separable Crossover-Promoting and Crossover-Constraining Aspects of Zip1 Activity during Budding Yeast Meiosis. PLoS Genet. 2015;11:e1005335 pubmed publisher
    ..an interspecies complementation experiment that reveals that the mature SC is dispensable for the formation of Mlh3-dependent crossovers in budding yeast...
  23. Testa E, Nardozi D, Antinozzi C, Faieta M, Di Cecca S, Caggiano C, et al. H2AFX and MDC1 promote maintenance of genomic integrity in male germ cells. J Cell Sci. 2018;131: pubmed publisher
    ..However, we observed that both genes play a similar role in the assembly of MLH3 onto chromosomes, a key step in crossover formation...
  24. Souliotis V, Vougas K, Gorgoulis V, Sfikakis P. Defective DNA repair and chromatin organization in patients with quiescent systemic lupus erythematosus. Arthritis Res Ther. 2016;18:182 pubmed publisher
    ..involved in DNA damage repair and signaling pathways, such as DDB1, ERCC2, XPA, XPC, MRE11A, RAD50, PARP1, MLH1, MLH3, and ATM were significantly underexpressed in SLE versus controls, whereas PPP1R15A, BARD1 and BBC3 genes ..
  25. Chakraborty P, Pankajam A, Lin G, Dutta A, Krishnaprasad N, Tekkedil M, et al. Modulating Crossover Frequency and Interference for Obligate Crossovers in Saccharomyces cerevisiae Meiosis. G3 (Bethesda). 2017;7:1511-1524 pubmed publisher
    ..previous studies have shown crossover frequencies are reduced in the mismatch repair related mutant mlh3? and enhanced in a meiotic checkpoint mutant pch2? by up to twofold at specific chromosomal loci, but ..
  26. Ghafouri Fard S, Fardaei M, Lankarani K, Miryounesi M. Segregation of a novel MLH1 mutation in an Iranian Lynch syndrome family. Gene. 2015;570:304-5 pubmed publisher
    ..Trp712Gly fs*71). This mutation is located in a region coding for the functional domain for the interaction with MLH3/PMS1/PMS2...
  27. Manhart C, Ni X, White M, Ortega J, Surtees J, Alani E. The mismatch repair and meiotic recombination endonuclease Mlh1-Mlh3 is activated by polymer formation and can cleave DNA substrates in trans. PLoS Biol. 2017;15:e2001164 pubmed publisher
    ..Recent genetic, biochemical, and molecular studies in yeast are consistent with the hypothesis of Mlh1-Mlh3 DNA mismatch repair complex acting as the major endonuclease activity that resolves dHJs into crossovers...
  28. Colas I, Macaulay M, Higgins J, Phillips D, Barakate A, Posch M, et al. A spontaneous mutation in MutL-Homolog 3 (HvMLH3) affects synapsis and crossover resolution in the barley desynaptic mutant des10. New Phytol. 2016;212:693-707 pubmed publisher
    ..in des10, a phenotype that was not evident with standard confocal microscopy and that has not been reported with Mlh3 knockout mutants in Arabidopsis...
  29. Kansal R, Li X, Shen J, Samuel D, Laningham F, Lee H, et al. An infant with MLH3 variants, FOXG1-duplication and multiple, benign cranial and spinal tumors: A clinical exome sequencing study. Genes Chromosomes Cancer. 2016;55:131-42 pubmed publisher
    ..359T>C;p.Phe120Ser and c.3344G>A;p.Arg1115Gln, in MLH3 (NM_001040108...
  30. Romaniuk Ð, Lyndin M, Smiyanov V, Sikora V, Rieznik A, Kuzenko Y, et al. Primary multiple tumor with affection of the thyroid gland, uterus, urinary bladder, mammary gland and other organs. Pathol Res Pract. 2017;213:574-579 pubmed publisher
    ..of Lynch syndrome for 100%, and its presence may be caused by the mutations of other genes (PMS1, PMS2 and MLH3), responsible for DNA repair. Unfortunately there wasn't any opportunity to study their mutations...
  31. Schmidt M, Pearson C. Disease-associated repeat instability and mismatch repair. DNA Repair (Amst). 2016;38:117-126 pubmed publisher
    ..of both the MMR proteins involved in disease repeat expansions, including: MSH2, MSH3, MSH6, MLH1, PMS2, and MLH3, as well as the types of repeats affected by MMR, now including: (CAG)·(CTG), (CGG)·(CCG), and (GAA)·(TTC) ..
  32. Freudenreich C. R-loops: targets for nuclease cleavage and repeat instability. Curr Genet. 2018;64:789-794 pubmed publisher
    ..were identified as causing R-loop-dependent breaks at CAG/CTG tracts: deamination of cytosines and the MutLγ (Mlh1-Mlh3) endonuclease, defining two new mechanisms for how R-loops can generate DNA breaks (Su and Freudenreich, Proc Natl ..
  33. Fischer J, Dudley S, Miller A, Liskay R. An intact Pms2 ATPase domain is not essential for male fertility. DNA Repair (Amst). 2016;39:46-51 pubmed publisher
    ..Meiotic analysis of knockout mice of two different MMR genes, Mlh1 and Mlh3, revealed both male and female infertility associated with a defect in meiotic crossing over...
  34. Kondo E, Horii A, Fukushige S. The interacting domains of three MutL heterodimers in man: hMLH1 interacts with 36 homologous amino acid residues within hMLH3, hPMS1 and hPMS2. Nucleic Acids Res. 2001;29:1695-702 pubmed
    ..Furthermore, we show that there is competition for the interacting domain in hMLH1 among the three other MutL homologues. Therefore, the quantitative balance of these three MutL heterodimers may be important in their functions. ..
  35. Ranjha L, Anand R, Cejka P. The Saccharomyces cerevisiae Mlh1-Mlh3 heterodimer is an endonuclease that preferentially binds to Holliday junctions. J Biol Chem. 2014;289:5674-86 pubmed publisher
    MutL?, a heterodimer of the MutL homologues Mlh1 and Mlh3, plays a critical role during meiotic homologous recombination...
  36. Ferrás C, Zhou X, Sousa M, Lindblom A, Barros A. DNA mismatch repair gene hMLH3 variants in meiotic arrest. Fertil Steril. 2007;88:1681-4 pubmed
  37. Erdeniz N, Nguyen M, DESCHENES S, Liskay R. Mutations affecting a putative MutLalpha endonuclease motif impact multiple mismatch repair functions. DNA Repair (Amst). 2007;6:1463-70 pubmed
    ..Thus, our in vivo results suggest that the endonuclease activity of MutLalpha is important not only in MMR-dependent mutation avoidance but also for recombination and damage response functions. ..
  38. Lenzi M, Smith J, Snowden T, Kim M, Fishel R, Poulos B, et al. Extreme heterogeneity in the molecular events leading to the establishment of chiasmata during meiosis i in human oocytes. Am J Hum Genet. 2005;76:112-27 pubmed
    ..chromosomes are fully paired, we find significant heterogeneity in the localization of the MutL homologs, MLH1 and MLH3, among human oocyte populations...
  39. Koessler T, Azzato E, Perkins B, Macinnis R, Greenberg D, Easton D, et al. Common germline variation in mismatch repair genes and survival after a diagnosis of colorectal cancer. Int J Cancer. 2009;124:1887-91 pubmed publisher
    ..We genotyped 2,060 patients for 68 SNPs in 7 mismatch repair genes (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2), using a single nucleotide polymorphism (SNP) tagging approach...
  40. Roesner L, Mielke C, Fähnrich S, Merkhoffer Y, Dittmar K, Drexler H, et al. Stable expression of MutL? in human cells reveals no specific response to mismatched DNA, but distinct recruitment to damage sites. J Cell Biochem. 2013;114:2405-14 pubmed publisher
    ..four MutL paralogues capable of forming heterodimeric MutL? (MLH1-PMS2), MutL? (MLH1-PMS1), and MutL? (MLH1-MLH3) protein complexes...
  41. Wu Y, Berends M, Sijmons R, Mensink R, Verlind E, Kooi K, et al. A role for MLH3 in hereditary nonpolyposis colorectal cancer. Nat Genet. 2001;29:137-8 pubmed
    We investigated a possible role of the mismatch-repair gene MLH3 in hereditary nonpolyposis colorectal cancer by scanning for mutations in 39 HNPCC families and in 288 patients suspected of having HNPCC...
  42. Michiels S, Danoy P, Dessen P, Bera A, Boulet T, Bouchardy C, et al. Polymorphism discovery in 62 DNA repair genes and haplotype associations with risks for lung and head and neck cancers. Carcinogenesis. 2007;28:1731-9 pubmed
    ..Haplotype analysis revealed potential associations (P < 0.05) between lung cancer and eight genes (MSH3, MLH3, POLK, LIG1, ERCC5, PMS1, POLG2 and RPA3) and between H-N cancer and four genes (PMS1, POLG2, POLR2B and RPA1) with ..
  43. Al Sweel N, Raghavan V, Dutta A, Ajith V, Di Vietro L, Khondakar N, et al. mlh3 mutations in baker's yeast alter meiotic recombination outcomes by increasing noncrossover events genome-wide. PLoS Genet. 2017;13:e1006974 pubmed publisher
    Mlh1-Mlh3 is an endonuclease hypothesized to act in meiosis to resolve double Holliday junctions into crossovers. It also plays a minor role in eukaryotic DNA mismatch repair (MMR)...
  44. Wojtczyk Miaskowska A, Presler M, Michajlowski J, Matuszewski M, Schlichtholz B. Gene Expression, DNA Methylation and Prognostic Significance of DNA Repair Genes in Human Bladder Cancer. Cell Physiol Biochem. 2017;42:2404-2417 pubmed publisher
    This study investigated the gene expression and DNA methylation of selected DNA repair genes (MBD4, TDG, MLH1, MLH3) and DNMT1 in human bladder cancer in the context of pathophysiological and prognostic significance...
  45. Su X, Freudenreich C. Cytosine deamination and base excision repair cause R-loop-induced CAG repeat fragility and instability in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2017;114:E8392-E8401 pubmed publisher
    ..Surprisingly, the MutL? (Mlh1/Mlh3) endonuclease caused R-loop-dependent CAG fragility, defining an alternative function for this complex...
  46. . Correction: mlh3 mutations in baker's yeast alter meiotic recombination outcomes by increasing noncrossover events genome-wide. PLoS Genet. 2017;13:e1007067 pubmed publisher
    ..This corrects the article DOI: 10.1371/journal.pgen.1006974.]...
  47. Jahid S, Sun J, Gelincik O, Blecua P, Edelmann W, Kucherlapati R, et al. Inhibition of colorectal cancer genomic copy number alterations and chromosomal fragile site tumor suppressor FHIT and WWOX deletions by DNA mismatch repair. Oncotarget. 2017;8:71574-71586 pubmed publisher
    ..DNA mismatch repair (MMR) inhibits HeR, but the roles of mammalian MMR MutL homologues (MLH1, PMS2 and MLH3) proteins in HeR suppression are poorly characterized...
  48. Duraturo F, Liccardo R, Izzo P. Coexistence of MLH3 germline variants in colon cancer patients belonging to families with Lynch syndrome-associated brain tumors. J Neurooncol. 2016;129:577-578 pubmed publisher
  49. Lipkin S, Wang V, Stoler D, Anderson G, Kirsch I, Hadley D, et al. Germline and somatic mutation analyses in the DNA mismatch repair gene MLH3: Evidence for somatic mutation in colorectal cancers. Hum Mutat. 2001;17:389-96 pubmed
    ..Our laboratory recently identified MLH3, a novel DNA mismatch repair gene...
  50. Xu K, Lu T, Zhou H, Bai L, Xiang Y. The role of MSH5 C85T and MLH3 C2531T polymorphisms in the risk of male infertility with azoospermia or severe oligozoospermia. Clin Chim Acta. 2010;411:49-52 pubmed publisher
    The mismatch repair proteins MSH5 and MLH3 play a crucial role in spermatogenesis. We tested this hypothesis by examining the contribution of functional polymorphisms in MSH5 C85T and MLH3 C2531T to the risk of male infertility.
  51. Santucci Darmanin S, Neyton S, Lespinasse F, Saunières A, Gaudray P, Paquis Flucklinger V. The DNA mismatch-repair MLH3 protein interacts with MSH4 in meiotic cells, supporting a role for this MutL homolog in mammalian meiotic recombination. Hum Mol Genet. 2002;11:1697-706 pubmed
    ..However, several MutS-like and MutL-like proteins also participate in meiotic recombination. The MutL homolog MLH3 has been recently identified in mammals...
  52. Markandona O, Dafopoulos K, Anifandis G, Messini C, Dimitraki M, Tsezou A, et al. Single-nucleotide polymorphism rs 175080 in the MLH3 gene and its relation to male infertility. J Assist Reprod Genet. 2015;32:1795-9 pubmed publisher
    b>MLH3, a MutL homolog protein in mammals playing a role in DNA mismatch repair, is associated with spermatogenesis and male infertility...
  53. Du J, Zhong M, Liu D, Liang S, Liu X, Cheng B, et al. Reduced MLH3 Expression in the Syndrome of Gan-Shen Yin Deficiency in Patients with Different Diseases. Evid Based Complement Alternat Med. 2017;2017:4109828 pubmed publisher
    ..However, considering all patients with PLC, HBP, and DM, only MLH3 was significantly lower in gan-shen Yin deficiency group than that in non-gen-shen Yin deficiency...
  54. Sherrington R, Rogaev E, Liang Y, Rogaeva E, Levesque G, Ikeda M, et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature. 1995;375:754-60 pubmed
    ..Because these changes occurred in conserved domains of this gene, and are not present in normal controls, they are likely to be causative of AD3. ..
  55. Smogorzewska A, Desetty R, Saito T, Schlabach M, Lach F, Sowa M, et al. A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease necessary for DNA interstrand crosslink repair. Mol Cell. 2010;39:36-47 pubmed publisher
    ..We propose that FAN1 is a repair nuclease that is recruited to sites of crosslink damage in part through binding the ubiquitinated ID complex through its UBZ domain. ..
  56. Kim J, Roh S, Yoon Y, Kim H, Park I. MLH3 and EXO1 alterations in familial colorectal cancer patients not fulfilling Amsterdam criteria. Cancer Genet Cytogenet. 2007;176:172-4 pubmed
  57. Iyer R, Pluciennik A, Genschel J, Tsai M, Beese L, Modrich P. MutLalpha and proliferating cell nuclear antigen share binding sites on MutSbeta. J Biol Chem. 2010;285:11730-9 pubmed publisher
    ..These findings also indicate that MutSbeta- and MutSalpha-initiated repair events differ in fundamental ways. ..
  58. Zelazowski M, Sandoval M, Paniker L, Hamilton H, Han J, Gribbell M, et al. Age-Dependent Alterations in Meiotic Recombination Cause Chromosome Segregation Errors in Spermatocytes. Cell. 2017;171:601-614.e13 pubmed publisher
    ..Analysis of recombination in the absence of MLH3 provides evidence for greater utilization in juveniles of pathways involving structure-selective nucleases and ..
  59. Song H, Ramus S, Quaye L, Dicioccio R, Tyrer J, Lomas E, et al. Common variants in mismatch repair genes and risk of invasive ovarian cancer. Carcinogenesis. 2006;27:2235-42 pubmed
    ..and 1531 cases from three separate studies were genotyped for 44 tagging SNPs (stSNP) in seven MMR genes (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2)...
  60. Lhotska H, Zemanova Z, Cechova H, Ransdorfova S, Lizcova L, Kramar F, et al. Genetic and epigenetic characterization of low-grade gliomas reveals frequent methylation of the MLH3 gene. Genes Chromosomes Cancer. 2015;54:655-67 pubmed publisher
    ..MutL homolog 3 (MLH3) promoter methylation was observed in 61% of LGO and 27% of LGA...
  61. Ye F, Cheng Q, Shen J, Zhou C, Chen H. Mismatch repair gene MLH3 Pro844Leu and Thr942Ile polymorphisms and the susceptibility to cervical carcinoma and HPV infection: a case-control study in a Chinese population. PLoS ONE. 2014;9:e96224 pubmed publisher
    To investigate the association between MLH3 Pro844Leu, Thr942Ile polymorphisms and potential linkage with the risk of cervical carcinoma and potential effect on protein function, we carried out a case-control study with 400 cervical ..
  62. van de Wijngaart D, Dubbink H, Molier M, de Vos C, Trapman J, Jenster G. Functional screening of FxxLF-like peptide motifs identifies SMARCD1/BAF60a as an androgen receptor cofactor that modulates TMPRSS2 expression. Mol Endocrinol. 2009;23:1776-86 pubmed publisher
    ..In summary, our data demonstrate that BAF60a directly interacts with the coactivator groove in the AR ligand-binding domain via its FxxFF motif, thereby selectively activating specific AR-driven promoters. ..
  63. Mann A, Hogdall E, Ramus S, Dicioccio R, Hogdall C, Quaye L, et al. Mismatch repair gene polymorphisms and survival in invasive ovarian cancer patients. Eur J Cancer. 2008;44:2259-65 pubmed publisher
    ..05) in seven MMR genes (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2) and survival of invasive ovarian cancer patients in three case-control studies ..
  64. Javid M, Sasanakietkul T, Nicolson N, Gibson C, Callender G, Korah R, et al. DNA Mismatch Repair Deficiency Promotes Genomic Instability in a Subset of Papillary Thyroid Cancers. World J Surg. 2018;42:358-366 pubmed publisher
    Efficient DNA damage repair by MutL-homolog DNA mismatch repair (MMR) enzymes, MLH1, MLH3, PMS1 and PMS2, are required to maintain thyrocyte genomic integrity...
  65. Lin X, Chen Z, Gao P, Gao Z, Chen H, Qi J, et al. TEX15: A DNA repair gene associated with prostate cancer risk in Han Chinese. Prostate. 2017;77:1271-1278 pubmed publisher
    ..24 (95% Confidence Interval 1.85-6.06), P?=?8.81?×?10-5 . Additionally, rs28756990 (V741F) at MLH3 (P?=?0.06) and rs2961144 (I126V) at OR2A5 (P?=?0...
  66. Koessler T, Oestergaard M, Song H, Tyrer J, Perkins B, Dunning A, et al. Common variants in mismatch repair genes and risk of colorectal cancer. Gut. 2008;57:1097-101 pubmed publisher
    ..A total of 2299 cases and 2284 unrelated controls were genotyped for 68 tagging SNPs in seven MMR genes (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2)...
  67. Korhonen M, Raevaara T, Lohi H, Nyström M. Conditional nuclear localization of hMLH3 suggests a minor activity in mismatch repair and supports its role as a low-risk gene in HNPCC. Oncol Rep. 2007;17:351-4 pubmed
    ..In absence of hPMS2, hMLH3 (hMutLgamma) is located in the nucleus, suggesting a conditional activity in MMR and supporting its role as a low-risk gene in HNPCC. ..