Gene Symbol: Mlh3
Description: mutL homolog 3
Alias: AV125803, BB126472, DNA mismatch repair protein Mlh3, mutL 3
Species: mouse
Products:     Mlh3

Top Publications

  1. Svetlanov A, Baudat F, Cohen P, de Massy B. Distinct functions of MLH3 at recombination hot spots in the mouse. Genetics. 2008;178:1937-45 pubmed publisher
    The four mammalian MutL homologs (MLH1, MLH3, PMS1, and PMS2) participate in a variety of events, including postreplicative DNA repair, prevention of homeologous recombination, and crossover formation during meiosis...
  2. 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
    MutL homolog 3 (Mlh3) is a member of a family of proteins conserved during evolution and having dual roles in DNA mismatch repair and meiosis...
  3. 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 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...
  4. 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
    ..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))...
  5. 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
    ..Four mammalian homologues of Escherichia coli MutL heterodimerize to form three distinct complexes: MLH1/PMS2, MLH1/MLH3, and MLH1/PMS1...
  6. 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. ..
  7. 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...
  8. Qiao H, Prasada Rao H, Yang Y, Fong J, Cloutier J, Deacon D, et al. Antagonistic roles of ubiquitin ligase HEI10 and SUMO ligase RNF212 regulate meiotic recombination. Nat Genet. 2014;46:194-9 pubmed publisher
    ..We suggest that SUMO and ubiquitin have antagonistic roles during meiotic recombination that are balanced to effect differential stabilization of recombination factors at crossover and non-crossover sites. ..
  9. 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. ..

More Information


  1. 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
    ..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...
  2. 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. ..
  3. 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 ..
  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. 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...
  6. Jahid S, Sun J, Edwards R, Dizon D, Panarelli N, Milsom J, et al. miR-23a promotes the transition from indolent to invasive colorectal cancer. Cancer Discov. 2012;2:540-53 pubmed publisher
    ..Analyses of computationally predicted target genes in microarray data sets of patients with colorectal cancers are consistent with a role for miR-23a, but not miR-27a, specifically in invasive colorectal cancers. ..
  7. 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
  8. 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...
  9. Zeng F, Baldwin D, Schultz R. Transcript profiling during preimplantation mouse development. Dev Biol. 2004;272:483-96 pubmed
    ..These results validate this hypothesis-generating approach by identifying genes involved in critical biological processes that can be the subject of a more traditional hypothesis-driven approach. ..
  10. Pinto R, Dragileva E, Kirby A, Lloret A, Lopez E, St Claire J, et al. Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches. PLoS Genet. 2013;9:e1003930 pubmed publisher
    ..Hdh(Q111) somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutL? (MLH1-MLH3) complex as a key driver of somatic expansion...
  11. 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 drastically ..
  12. Li X, Li X, Schimenti J. Mouse pachytene checkpoint 2 (trip13) is required for completing meiotic recombination but not synapsis. PLoS Genet. 2007;3:e130 pubmed
    ..These chromosomes also exhibited the chiasmata markers MLH1 and MLH3, and okadaic acid treatment of mutant spermatocytes caused progression to metaphase I with bivalent chromosomes...
  13. Wu X, Tsai C, Patam M, Zan H, Chen J, Lipkin S, et al. A role for the MutL mismatch repair Mlh3 protein in immunoglobulin class switch DNA recombination and somatic hypermutation. J Immunol. 2006;176:5426-37 pubmed
    ..The MutL homolog Mlh3 is the last complement of the mammalian set of MMR proteins...
  14. Li Z, Peled J, Zhao C, Svetlanov A, Ronai D, Cohen P, et al. A role for Mlh3 in somatic hypermutation. DNA Repair (Amst). 2006;5:675-82 pubmed
    ..The MutL homolog MLH3 has been implicated in meiosis and DNA mismatch repair (MMR)...