Mlh1

Summary

Gene Symbol: Mlh1
Description: mutL homolog 1
Alias: 1110035C23Rik, AI317206, AI325952, AI561766, DNA mismatch repair protein Mlh1, colon cancer, nonpolyposis type 2, mutL protein homolog 1
Species: mouse
Products:     Mlh1

Top Publications

  1. Schrader C, Vardo J, Stavnezer J. Role for mismatch repair proteins Msh2, Mlh1, and Pms2 in immunoglobulin class switching shown by sequence analysis of recombination junctions. J Exp Med. 2002;195:367-73 pubmed
    ..demonstrate clear differences in the sequences of switch junctions in wild-type B cells in comparison with Msh2-, Mlh1-, and Pms2-deficient B cells...
  2. Sansom O, Bishop S, Court H, Dudley S, Liskay R, Clarke A. Apoptosis and mutation in the murine small intestine: loss of Mlh1- and Pms2-dependent apoptosis leads to increased mutation in vivo. DNA Repair (Amst). 2003;2:1029-39 pubmed
    ..Here, we extend these studies to the MutL homologues (MLH) Mlh1 and Pms2 by analysing the apoptotic response within the small intestine of gene targeted strains...
  3. Kolas N, Svetlanov A, Lenzi M, Macaluso F, Lipkin S, Liskay R, et al. Localization of MMR proteins on meiotic chromosomes in mice indicates distinct functions during prophase I. J Cell Biol. 2005;171:447-58 pubmed
    ..Mutations of three of the four MutL homologues (Mlh1, Mlh3, and Pms2) result in meiotic defects...
  4. Reynolds A, Qiao H, Yang Y, Chen J, Jackson N, Biswas K, et al. RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosis. Nat Genet. 2013;45:269-78 pubmed publisher
    ..Haploinsufficiency indicates that RNF212 is a limiting factor for crossover control and raises the possibility that human alleles may alter the amount or stability of RNF212 and be risk factors for aneuploid conditions. ..
  5. Yoshioka K, Yoshioka Y, Hsieh P. ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Mol Cell. 2006;22:501-10 pubmed
    ..These results suggest that MMR proteins can act as direct sensors of methylation damage and help recruit ATR-ATRIP to sites of cytotoxic O(6)-meG adducts to initiate ATR checkpoint signaling. ..
  6. Bronner C, Baker S, Morrison P, Warren G, Smith L, Lescoe M, et al. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature. 1994;368:258-61 pubmed
    ..gene located on 3p because of the similarity of the hMLH1 gene product to the yeast DNA mismatch repair protein, MLH1, the coincident location of the hMLH1 gene and the HNPCC locus on chromosome 3, and hMLH1 missense mutations in ..
  7. Schramm S, Fraune J, Naumann R, Hernández Hernández A, Hoog C, Cooke H, et al. A novel mouse synaptonemal complex protein is essential for loading of central element proteins, recombination, and fertility. PLoS Genet. 2011;7:e1002088 pubmed publisher
    ..recombination appears to be normal, but its progression is severely impaired resulting in complete absence of MLH1 foci, which are presumed markers of crossovers in wild-type meiocytes...
  8. Celeste A, Petersen S, Romanienko P, Fernandez Capetillo O, Chen H, Sedelnikova O, et al. Genomic instability in mice lacking histone H2AX. Science. 2002;296:922-7 pubmed
    ..Thus, H2AX is critical for facilitating the assembly of specific DNA-repair complexes on damaged DNA. ..
  9. Di Giacomo M, Barchi M, Baudat F, Edelmann W, Keeney S, Jasin M. Distinct DNA-damage-dependent and -independent responses drive the loss of oocytes in recombination-defective mouse mutants. Proc Natl Acad Sci U S A. 2005;102:737-42 pubmed
    ..The absence of ATM caused defects in folliculogenesis that were similar to those in Dmc1 mutants and that could be suppressed by Spo11 mutation, implying that oocyte death in Atm-deficient animals is a response to defective DSB repair...

More Information

Publications78

  1. Guillon H, Baudat F, Grey C, Liskay R, de Massy B. Crossover and noncrossover pathways in mouse meiosis. Mol Cell. 2005;20:563-73 pubmed
    ..and NCRs require Spo11, NCR products have shorter conversion tracts than CRs, and only CRs require the MutL homolog Mlh1. We show that both products are formed from middle to late pachytene of meiotic prophase and provide evidence for ..
  2. Kuramochi Miyagawa S, Kimura T, Ijiri T, Isobe T, Asada N, Fujita Y, et al. Mili, a mammalian member of piwi family gene, is essential for spermatogenesis. Development. 2004;131:839-49 pubmed
    ..These data indicate that MILI is essential for the differentiation of spermatocytes. ..
  3. Kan R, Sun X, Kolas N, Avdievich E, Kneitz B, Edelmann W, et al. Comparative analysis of meiotic progression in female mice bearing mutations in genes of the DNA mismatch repair pathway. Biol Reprod. 2008;78:462-71 pubmed
    ..of oocytes through prophase I and the meiotic divisions in mice harboring deletions in members of the MMR pathway (Mlh1, Mlh3, Exo1, and an ATPase-deficient variant of Mlh1, Mlh1(G67R))...
  4. Daniel K, Lange J, Hached K, Fu J, Anastassiadis K, Roig I, et al. Meiotic homologue alignment and its quality surveillance are controlled by mouse HORMAD1. Nat Cell Biol. 2011;13:599-610 pubmed publisher
  5. Phung Q, Winter D, Alrefai R, Gearhart P. Hypermutation in Ig V genes from mice deficient in the MLH1 mismatch repair protein. J Immunol. 1999;162:3121-4 pubmed
    ..PMS2 produced different mutational spectra, we examined the role of another protein involved in mismatch repair, MLH1, on the frequency and pattern of hypermutation...
  6. Edelmann W, Yang K, Kuraguchi M, Heyer J, Lia M, Kneitz B, et al. Tumorigenesis in Mlh1 and Mlh1/Apc1638N mutant mice. Cancer Res. 1999;59:1301-7 pubmed
    An3 1 KAL I MutL homologue 1 (MLH1) is a member of the family of proteins required for DNA mismatch repair. Germ-line mutations in MLH1 lead to the cancer susceptibility syndrome hereditary nonpolyposis colorectal cancer (HNPCC)...
  7. Holloway J, Mohan S, Balmus G, Sun X, Modzelewski A, Borst P, et al. Mammalian BTBD12 (SLX4) protects against genomic instability during mammalian spermatogenesis. PLoS Genet. 2011;7:e1002094 pubmed publisher
    ..resulting in persistent ?H2AX and RAD51, and the choice of repair pathway may be altered, resulting in elevated MLH1/MLH3 focus numbers at pachynema. The result is an increase in apoptosis through prophase I and beyond...
  8. Kim N, Bozek G, Lo J, Storb U. Different mismatch repair deficiencies all have the same effects on somatic hypermutation: intact primary mechanism accompanied by secondary modifications. J Exp Med. 1999;190:21-30 pubmed
    ..In this study, we have analyzed somatic hypermutation in two MutL types of MMR deficiencies, Pms2 and Mlh1. The mutation target was a nonselectable Ig-kappa gene with an artificial insert in the V region...
  9. Baker S, Plug A, Prolla T, Bronner C, Harris A, Yao X, et al. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat Genet. 1996;13:336-42 pubmed
    ..Here mice deficient in another mismatch repair gene, Mlh1, possess not only microsatellite instability but are also infertile (both males and females)...
  10. Chen P, Dudley S, Hagen W, Dizon D, Paxton L, Reichow D, et al. Contributions by MutL homologues Mlh3 and Pms2 to DNA mismatch repair and tumor suppression in the mouse. Cancer Res. 2005;65:8662-70 pubmed
    Germ line DNA mismatch repair mutations in MLH1 and MSH2 underlie the vast majority of hereditary non-polyposis colon cancer...
  11. Taniguchi K, Kakinuma S, Tokairin Y, Arai M, Kohno H, Wakabayashi K, et al. Mild inflammation accelerates colon carcinogenesis in Mlh1-deficient mice. Oncology. 2006;71:124-30 pubmed
    Inflammatory bowel disease, which frequently accompanies silencing of Mlh1, plays a key role in the pathogenesis of colorectal cancer. The interaction between inflammation and mismatch repair deficiency, however, remains unclear...
  12. Schrader C, Guikema J, Linehan E, Selsing E, Stavnezer J. Activation-induced cytidine deaminase-dependent DNA breaks in class switch recombination occur during G1 phase of the cell cycle and depend upon mismatch repair. J Immunol. 2007;179:6064-71 pubmed
    ..We also show that nucleotide excision repair does not contribute to class switching. Our data support the hypothesis that MMR is required to convert SSBs into DSBs when SSBs on opposite strands are too distal to form DSBs spontaneously. ..
  13. Frumkin D, Wasserstrom A, Itzkovitz S, Stern T, Harmelin A, Eilam R, et al. Cell lineage analysis of a mouse tumor. Cancer Res. 2008;68:5924-31 pubmed publisher
  14. Lipkin S, Moens P, Wang V, Lenzi M, Shanmugarajah D, Gilgeous A, et al. Meiotic arrest and aneuploidy in MLH3-deficient mice. Nat Genet. 2002;31:385-90 pubmed
    ..Of the four MutL homologs, Mlh1, Mlh3, Pms1 and Pms2, three are involved in mismatch repair and at least two, Pms2 and Mlh1, are essential for ..
  15. Schrader C, Edelmann W, Kucherlapati R, Stavnezer J. Reduced isotype switching in splenic B cells from mice deficient in mismatch repair enzymes. J Exp Med. 1999;190:323-30 pubmed
    ..Splenic B cells from mice deficient in Msh2, Mlh1, Pms2, or Mlh1 and Pms2 were stimulated in culture with lipopolysaccharide (LPS) to induce immunoglobulin (Ig)G2b ..
  16. Wu X, Platt J, Cascalho M. Dimerization of MLH1 and PMS2 limits nuclear localization of MutLalpha. Mol Cell Biol. 2003;23:3320-8 pubmed
    ..Since the functions of mismatch repair are initiated in the nucleus, we asked whether nuclear transport of MLH1 and PMS2 is limiting for the nuclear localization of MutLalpha (the MLH1-PMS2 dimer)...
  17. Holloway J, Booth J, Edelmann W, McGowan C, Cohen P. MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis. PLoS Genet. 2008;4:e1000186 pubmed publisher
    ..for processing double-strand breaks (DSBs) as crossovers have been described, one dependent on the MutL homologs Mlh1 and Mlh3, and the other on the structure-specific endonuclease Mus81...
  18. Herrán Y, Gutiérrez Caballero C, Sanchez Martin M, Hernandez T, Viera A, Barbero J, et al. The cohesin subunit RAD21L functions in meiotic synapsis and exhibits sexual dimorphism in fertility. EMBO J. 2011;30:3091-105 pubmed publisher
    ..Thus, our results provide in vivo evidence that RAD21L is essential for male fertility and in females for the maintenance of fertility during natural aging. ..
  19. Eccleston J, Yan C, Yuan K, Alt F, Selsing E. Mismatch repair proteins MSH2, MLH1, and EXO1 are important for class-switch recombination events occurring in B cells that lack nonhomologous end joining. J Immunol. 2011;186:2336-43 pubmed publisher
    ..Our results show that MLH1, EXO1, and MSH2 are all important for efficient A-EJ-mediated CSR, and we propose that MMR proteins convert DNA ..
  20. Avdievich E, Reiss C, Scherer S, Zhang Y, Maier S, Jin B, et al. Distinct effects of the recurrent Mlh1G67R mutation on MMR functions, cancer, and meiosis. Proc Natl Acad Sci U S A. 2008;105:4247-52 pubmed publisher
    Mutations in the human DNA mismatch repair (MMR) gene MLH1 are associated with hereditary nonpolyposis colorectal cancer (Lynch syndrome, HNPCC) and a significant proportion of sporadic colorectal cancer...
  21. Hamer G, Gell K, Kouznetsova A, Novak I, Benavente R, Hoog C. Characterization of a novel meiosis-specific protein within the central element of the synaptonemal complex. J Cell Sci. 2006;119:4025-32 pubmed
    ..SYCE1 interacts more directly with SYCP1 and could thus anchor the central element proteins to the transverse filaments. ..
  22. van de Vrugt H, Eaton L, Hanlon Newell A, Al Dhalimy M, Liskay R, Olson S, et al. Embryonic lethality after combined inactivation of Fancd2 and Mlh1 in mice. Cancer Res. 2009;69:9431-8 pubmed publisher
    ..the consequences of combined Fanconi anemia (FA) and mismatch repair pathway inactivation, defects in Fancd2 and Mlh1 were combined in one mouse model...
  23. Kouznetsova A, Benavente R, Pastink A, Hoog C. Meiosis in mice without a synaptonemal complex. PLoS ONE. 2011;6:e28255 pubmed publisher
    ..In contrast, in SC-null meiocytes synapsis and MLH1-MLH3-dependent crossovers maturation were abolished, whereas the structural integrity of chromosomes was ..
  24. Edelmann W, Cohen P, Kane M, Lau K, Morrow B, Bennett S, et al. Meiotic pachytene arrest in MLH1-deficient mice. Cell. 1996;85:1125-34 pubmed
    Germ line mutations in DNA mismatch repair genes including MLH1 cause hereditary nonpolyposis colon cancer. To understand the role of MLH1 in normal growth and development, we generated mice that have a null mutation of this gene...
  25. Woods L, Hodges C, Baart E, Baker S, Liskay M, Hunt P. Chromosomal influence on meiotic spindle assembly: abnormal meiosis I in female Mlh1 mutant mice. J Cell Biol. 1999;145:1395-406 pubmed
    ..meiotic spindle in murine oocytes from mice homozygous for a targeted disruption of the DNA mismatch repair gene, Mlh1. In the absence of the MLH1 protein meiotic recombination is dramatically reduced and, as a result, the vast ..
  26. Eaker S, Cobb J, Pyle A, Handel M. Meiotic prophase abnormalities and metaphase cell death in MLH1-deficient mouse spermatocytes: insights into regulation of spermatogenic progress. Dev Biol. 2002;249:85-95 pubmed
    The MLH1 protein is required for normal meiosis in mice and its absence leads to failure in maintenance of pairing between bivalent chromosomes, abnormal meiotic division, and ensuing sterility in both sexes...
  27. Yang F, Gell K, van der Heijden G, Eckardt S, Leu N, Page D, et al. Meiotic failure in male mice lacking an X-linked factor. Genes Dev. 2008;22:682-91 pubmed publisher
    ..Thus, TEX11 promotes initiation and/or maintenance of synapsis and formation of crossovers, and may provide a physical link between these two meiotic processes. ..
  28. Albertson T, Ogawa M, Bugni J, Hays L, Chen Y, Wang Y, et al. DNA polymerase epsilon and delta proofreading suppress discrete mutator and cancer phenotypes in mice. Proc Natl Acad Sci U S A. 2009;106:17101-4 pubmed publisher
    ..These findings distinguish Pol epsilon and delta functions in vivo and reveal tissue-specific requirements for DNA replication fidelity. ..
  29. Moens P, Marcon E, Shore J, Kochakpour N, Spyropoulos B. Initiation and resolution of interhomolog connections: crossover and non-crossover sites along mouse synaptonemal complexes. J Cell Sci. 2007;120:1017-27 pubmed
    ..Immunogold electron microscope evidence shows that one or two TNs of the 10-15 TNs per SC acquire MLH1 protein, the hallmark of reciprocal recombination, whereas the TNs that do not acquire MLH1 protein relocate from ..
  30. Kneitz B, Cohen P, Avdievich E, Zhu L, Kane M, Hou H, et al. MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice. Genes Dev. 2000;14:1085-97 pubmed
    ..Our results show that MSH4 localization on chromosomes during the early stages of meiosis is essential for normal chromosome synapsis in prophase I and that it acts in the same pathway as MSH5. ..
  31. Nagaoka S, Hodges C, Albertini D, HUNT P. Oocyte-specific differences in cell-cycle control create an innate susceptibility to meiotic errors. Curr Biol. 2011;21:651-7 pubmed publisher
    ..The present study of Mlh1 mutant mice demonstrates that metaphase alignment is not a prerequisite for anaphase onset and provides strong ..
  32. Prolla T, Baker S, Harris A, Tsao J, Yao X, Bronner C, et al. Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DNA mismatch repair. Nat Genet. 1998;18:276-9 pubmed
    Germline mutations in the human MSH2, MLH1, PMS2 and PMS1 DNA mismatch repair (MMR) gene homologues appear to be responsible for most cases of hereditary non-polyposis colorectal cancer (HNPCC; refs 1-5)...
  33. Kolas N, Cohen P. Novel and diverse functions of the DNA mismatch repair family in mammalian meiosis and recombination. Cytogenet Genome Res. 2004;107:216-31 pubmed
    ..These studies highlight the importance of comparative analysis of MMR orthologs across species, and also underscore distinct sexually dimorphic characteristics of mammalian recombination and meiosis. ..
  34. Zechmeister Machhart M, Hufnagl P, Uhrin P, Xu J, Geiger M, Binder B. Molecular cloning and tissue distribution of mouse protein C inhibitor (PCI). Immunopharmacology. 1996;32:96-8 pubmed
  35. Chesnokova V, Wong C, Zonis S, Gruszka A, Wawrowsky K, Ren S, et al. Diminished pancreatic beta-cell mass in securin-null mice is caused by beta-cell apoptosis and senescence. Endocrinology. 2009;150:2603-10 pubmed publisher
    ..Our results also suggest that ductal progenitor beta-cells are exhausted by excessive neogenesis induced by apoptosis in PTTG(-/-) mice. ..
  36. Ren G, Zhao X, Wang Y, Zhang X, Chen X, Xu C, et al. CCR2-dependent recruitment of macrophages by tumor-educated mesenchymal stromal cells promotes tumor development and is mimicked by TNF?. Cell Stem Cell. 2012;11:812-24 pubmed publisher
    ..Therefore, our findings demonstrate that, in an inflammatory environment, tumor-resident MSCs promote tumor growth by recruiting monocytes/macrophages. ..
  37. Cunto F, Imarisio S, Camera P, Boitani C, Altruda F, Silengo L. Essential role of citron kinase in cytokinesis of spermatogenic precursors. J Cell Sci. 2002;115:4819-26 pubmed
    ..The same cells display a severe cytokinesis defect, resulting in the production of multinucleated cells and apoptosis. Our data indicate that Citron kinase is specifically required for cytokinesis of the male germ line. ..
  38. Elliott E, Sheaffer K, Schug J, Stappenbeck T, Kaestner K. Dnmt1 is essential to maintain progenitors in the perinatal intestinal epithelium. Development. 2015;142:2163-72 pubmed publisher
    ..These results demonstrate an essential role for Dnmt1 in maintaining genomic stability during intestinal development and the establishment of intestinal crypts. ..
  39. Itano O, Yang K, Fan K, Kurihara N, Shinozaki H, Abe S, et al. Sulindac effects on inflammation and tumorigenesis in the intestine of mice with Apc and Mlh1 mutations. Carcinogenesis. 2009;30:1923-6 pubmed publisher
    ..tumorigenesis; these were (i) Apc(1638N/+) mouse (chain termination mutation in exon 15 of the Apc gene); (ii) Mlh1(+/-) mouse (DNA mismatch repair deficiency, a mouse model of human hereditary non-polyposis colorectal cancer) and (..
  40. Collins S, Hervé R, Keevil C, Blaydes J, Webb J. Down-regulation of DNA mismatch repair enhances initiation and growth of neuroblastoma and brain tumour multicellular spheroids. PLoS ONE. 2011;6:e28123 pubmed publisher
    ..Analysis of the DNA MMR genes MLH1 and PMS2 revealed both to be significantly down-regulated at the mRNA level compared with non-spheroid-forming ..
  41. Reizel Y, Itzkovitz S, Adar R, Elbaz J, Jinich A, Chapal Ilani N, et al. Cell lineage analysis of the mammalian female germline. PLoS Genet. 2012;8:e1002477 pubmed publisher
    ..Overall, our study sheds light on substantial novel aspects of female germline preservation and development. ..
  42. Tsao J, Dudley S, Kwok B, Nickel A, Laird P, Siegmund K, et al. Diet, cancer and aging in DNA mismatch repair deficient mice. Carcinogenesis. 2002;23:1807-10 pubmed
    ..b>Mlh1 deficient mice are prone to lymphomas and intestinal adenomas and carcinomas...
  43. Kabbarah O, Sotelo A, Mallon M, Winkeler E, Fan M, Pfeifer J, et al. Diethylstilbestrol effects and lymphomagenesis in Mlh1-deficient mice. Int J Cancer. 2005;115:666-9 pubmed
    ..to model endometrial carcinoma associated with mutation in MMR, we treated mice carrying knockout alleles for Mlh1 or Msh2 with the synthetic estrogen diethylstilbestrol (DES), a known promoter of uterine endometrial carcinoma...
  44. He W, Zhao Y, Zhang C, An L, Hu Z, Liu Y, et al. Rad9 plays an important role in DNA mismatch repair through physical interaction with MLH1. Nucleic Acids Res. 2008;36:6406-17 pubmed publisher
    ..In this study, we have demonstrated that both human and mouse Rad9 interacts physically with the MMR protein MLH1. Disruption of the interaction by a single-point mutation in Rad9 leads to significantly reduced MMR activity...
  45. Grigera F, Bellacosa A, Kenter A. Complex relationship between mismatch repair proteins and MBD4 during immunoglobulin class switch recombination. PLoS ONE. 2013;8:e78370 pubmed publisher
    ..Methyl CpG binding domain protein 4 (MBD4) binds to MutL homologue 1 (MLH1) and controls the post-transcriptional level of several MMR proteins, including MutS homologue 2 (MSH2)...
  46. Fang Y, Tsao C, Goodman B, Furumai R, Tirado C, Abraham R, et al. ATR functions as a gene dosage-dependent tumor suppressor on a mismatch repair-deficient background. EMBO J. 2004;23:3164-74 pubmed
    ..Monoallelic ATR gene targeting in MLH1-deficient HCT 116 colon carcinoma cells resulted in hypersensitivity to genotoxic stress accompanied by dramatic ..
  47. Kawate H, Itoh R, Sakumi K, Nakabeppu Y, Tsuzuki T, Ide F, et al. A defect in a single allele of the Mlh1 gene causes dissociation of the killing and tumorigenic actions of an alkylating carcinogen in methyltransferase-deficient mice. Carcinogenesis. 2000;21:301-5 pubmed
    Mice with mutations in both alleles of the Mgmt and the Mlh1 gene, the former encoding a DNA repair methyltransferase and the latter a protein functioning at an early step of mismatch repair, are as resistant to the killing action of ..
  48. Holloway J, Sun X, Yokoo R, Villeneuve A, Cohen P. Mammalian CNTD1 is critical for meiotic crossover maturation and deselection of excess precrossover sites. J Cell Biol. 2014;205:633-41 pubmed publisher
  49. Malki S, van der Heijden G, O Donnell K, Martin S, Bortvin A. A role for retrotransposon LINE-1 in fetal oocyte attrition in mice. Dev Cell. 2014;29:521-533 pubmed publisher
    ..We propose that FOA serves to select oocytes with limited L1 activity that are therefore best suited for the next generation...
  50. Fu Z, Regan K, Zhang L, Muders M, Thibodeau S, French A, et al. Deficiencies in Chfr and Mlh1 synergistically enhance tumor susceptibility in mice. J Clin Invest. 2009;119:2714-24 pubmed publisher
    ..Mice with deficiencies in both Chfr and Mlh1 (the gene that encodes the DNA mismatch-repair protein Mlh1) displayed dramatically higher incidence of spontaneous ..
  51. Chahwan R, van Oers J, Avdievich E, Zhao C, Edelmann W, Scharff M, et al. The ATPase activity of MLH1 is required to orchestrate DNA double-strand breaks and end processing during class switch recombination. J Exp Med. 2012;209:671-8 pubmed publisher
    ..b>MLH1, an ATPase member of the mismatch repair (MMR) machinery, is emerging as a likely regulator of whether a U:G ..
  52. Takagi Y, Takahashi M, Sanada M, Ito R, Yamaizumi M, Sekiguchi M. Roles of MGMT and MLH1 proteins in alkylation-induced apoptosis and mutagenesis. DNA Repair (Amst). 2003;2:1135-46 pubmed
    ..lines defective in the Mgmt gene encoding a DNA repair enzyme, O(6)-methylguanine-DNA methyltransferase, and/or the Mlh1 gene encoding a protein involved in mismatch repair were established from gene-targeted mice...
  53. Reed K, Sansom O, Hayes A, Gescher A, Peters J, Clarke A. PPARdelta status and mismatch repair mediated neoplasia in the mouse intestine. BMC Cancer. 2006;6:113 pubmed
    ..Mice deficient for both PPARdelta and the mismatch repair gene Mlh1 were produced and the incidence and severity of intestinal neoplasia recorded...
  54. Stadthagen G, Tehler D, Høyland Kroghsbo N, Wen J, Krogh A, Jensen K, et al. Loss of miR-10a activates lpo and collaborates with activated Wnt signaling in inducing intestinal neoplasia in female mice. PLoS Genet. 2013;9:e1003913 pubmed publisher
    ..This suggests that miR-10a could be used as a potent diagnostic marker for discovering groups of women that are at high risk of developing colorectal carcinoma, which today is one of the leading causes of cancer-related deaths. ..
  55. Liebe B, Petukhova G, Barchi M, Bellani M, Braselmann H, Nakano T, et al. Mutations that affect meiosis in male mice influence the dynamics of the mid-preleptotene and bouquet stages. Exp Cell Res. 2006;312:3768-81 pubmed
    ..spermatocytes were significantly increased in male mice lacking recombination proteins SPO11, MEI1, MLH1, KU80, ubiquitin conjugating enzyme HR6B, and in mice with only one copy of the telomere length regulator Terf1...
  56. Blake C, Tsao J, Wu A, Shibata D. Stepwise deletions of polyA sequences in mismatch repair-deficient colorectal cancers. Am J Pathol. 2001;158:1867-70 pubmed
    ..but less extensive total deletions (maximum of -12 bp) occurred in similar polyA sequences in MMR-deficient mice (mlh1-/-) up to 478 days old...
  57. Shao C, Deng L, Chen Y, Kucherlapati R, Stambrook P, Tischfield J. Mlh1 mediates tissue-specific regulation of mitotic recombination. Oncogene. 2004;23:9017-24 pubmed
    ..Thus, relatively small genetic differences are capable of restricting MR in a tissue-specific manner. Using Mlh1-deficient mice, we tested the role of mismatch repair in MR in two isogenic cell types...
  58. Gutmann D, Winkeler E, Kabbarah O, Hedrick N, Dudley S, Goodfellow P, et al. Mlh1 deficiency accelerates myeloid leukemogenesis in neurofibromatosis 1 (Nf1) heterozygous mice. Oncogene. 2003;22:4581-5 pubmed
    ..To evaluate the contribution of Mlh1 MMR deficiency to Nf1 tumorigenesis, Mlh1-/-;Nf1+/- mice were generated...
  59. Bardwell P, Woo C, Wei K, Li Z, Martin A, Sack S, et al. Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice. Nat Immunol. 2004;5:224-9 pubmed
    ..The phenotype of Exo1(-/-) mice and the finding that Exo1 and Mlh1 are physically associated with mutating variable regions support the idea that Exo1 and MMR participate directly in ..
  60. Cherry S, Adelman C, Theunissen J, Hassold T, Hunt P, Petrini J. The Mre11 complex influences DNA repair, synapsis, and crossing over in murine meiosis. Curr Biol. 2007;17:373-8 pubmed
    ..chromosomes, persistence of strand exchange proteins, and alterations in both the frequency and placement of MLH1 foci, a marker of crossovers...
  61. Kogo H, Tsutsumi M, Ohye T, Inagaki H, Abe T, Kurahashi H. HORMAD1-dependent checkpoint/surveillance mechanism eliminates asynaptic oocytes. Genes Cells. 2012;17:439-54 pubmed publisher
    ..Our present results provide clues to HORMAD1-dependent checkpoint in response to asynapsis in mammalian meiosis...
  62. Smith Roe S, Hegan D, Glazer P, Buermeyer A. Mlh1-dependent suppression of specific mutations induced in vivo by the food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP). Mutat Res. 2006;594:101-12 pubmed
    ..We determined the effect of MMR status (Mlh1+/+ versus Mlh1-/-) on mutagenesis induced by the cooked-meat mutagen, 2-amino-1-methyl-6-phenylimidazo [4,5-b] ..
  63. Ghodgaonkar M, Lazzaro F, Olivera Pimentel M, Artola Borán M, Cejka P, Reijns M, et al. Ribonucleotides misincorporated into DNA act as strand-discrimination signals in eukaryotic mismatch repair. Mol Cell. 2013;50:323-32 pubmed publisher
    ..fragment termini in the lagging strand and at nicks generated in the leading strand by the mismatch-activated MLH1/PMS2 endonuclease...
  64. Pandey R, Tokuzawa Y, Yang Z, Hayashi E, Ichisaka T, Kajita S, et al. Tudor domain containing 12 (TDRD12) is essential for secondary PIWI interacting RNA biogenesis in mice. Proc Natl Acad Sci U S A. 2013;110:16492-7 pubmed publisher
    ..Cell-culture studies with the insect ortholog of TDRD12 suggest a role for the multidomain protein in mediating complex formation with other participants during secondary piRNA biogenesis. ..
  65. Peltomaki P. DNA mismatch repair and cancer. Mutat Res. 2001;488:77-85 pubmed
    ..A brief overview of these different features of the human DNA mismatch repair system will be provided, with the emphasis in their implications in cancer development. ..
  66. Kuniyasu H, Sasaki T, Sasahira T, Chihara Y, Ohmori H. Repression of MLH1 and MGMT genes in colon mucosa adjacent to implanted cancer in athymic mouse. J Exp Clin Cancer Res. 2004;23:317-23 pubmed
    ..mucosa adjacent to KM12SM tumors in the cecum of athymic mice, reductions in the levels of the mutL homologue 1 (MLH1) and O6-methylguanine-DNA methyltransferase (MGMT) proteins were detected by immunohistochemistry and ..
  67. Bacher J, Abdel Megid W, Kent First M, Halberg R. Use of mononucleotide repeat markers for detection of microsatellite instability in mouse tumors. Mol Carcinog. 2005;44:285-92 pubmed
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