mutl protein homolog 1


Summary: Eukaryotic homolog of the bacterial MutL DNA MISMATCH REPAIR protein. It heterodimerizes with MISMATCH REPAIR ENDONUCLEASE PMS2 to form MutL alpha, which is recruited to DNA mismatch sites by the MUTS DNA MISMATCH-BINDING PROTEIN. Mutations in the human MLH1 gene are associated with COLORECTAL NEOPLASMS, HEREDITARY NONPOLYPOSIS.

Top Publications

  1. Cosgrove C, Cohn D, Hampel H, Frankel W, Jones D, McElroy J, et al. Epigenetic silencing of MLH1 in endometrial cancers is associated with larger tumor volume, increased rate of lymph node positivity and reduced recurrence-free survival. Gynecol Oncol. 2017;146:588-595 pubmed publisher
    ..MMR testing that includes MLH1 methylation analysis defines a subset of tumors that have worse prognostic features and reduced RFS. ..
  2. Takahashi K, Sato N, Sugawara T, Kato A, Sato T, Shimizu D, et al. Clinical characteristics of Lynch-like cases collaterally classified by Lynch syndrome identification strategy using universal screening in endometrial cancer. Gynecol Oncol. 2017;147:388-395 pubmed publisher
    ..5% vs. 38.6% and 47.1% vs. 25.2%, respectively). Herein, we report the features of LL classified by LS identification via U/S in Asian EC. LL should be candidates for tailored surveillance based on regionality and family history. ..
  3. 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
    ..Together these observations argue that Mlh1-Mlh3 may not act like a canonical, RuvC-like Holliday junction resolvase and support a novel model in which Mlh1-Mlh3 is loaded onto DNA to form an activated polymer that cleaves DNA. ..
  4. . Identification of Genetic Factors that Modify Clinical Onset of Huntington's Disease. Cell. 2015;162:516-26 pubmed publisher
    ..Our findings demonstrate that HD disease modification in humans occurs in nature and offer a genetic route to identifying in-human validated therapeutic targets in this and other Mendelian disorders. ..
  5. Ricker C, Hanna D, Peng C, Nguyen N, Stern M, Schmit S, et al. DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer. Cancer. 2017;123:3732-3743 pubmed publisher
    ..Cancer 2017. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. Cancer 2017;123:3732-3743. © 2017 American Cancer Society. ..
  6. Zhao J, Li X, Shi B, Wang F, Xu Z, Meng H, et al. Effect of histone modifications on hMLH1 alternative splicing in gastric cancer. Tumour Biol. 2017;39:1010428317697546 pubmed publisher
    ..SRSF2 may be involved in these specific exons skipping as well. ..
  7. Clendenning M, Macrae F, Walsh M, Walters R, Thibodeau S, Gunawardena S, et al. Absence of PMS2 mutations in colon-CFR participants whose colorectal cancers demonstrate unexplained loss of MLH1 expression. Clin Genet. 2013;83:591-3 pubmed publisher
  8. Ruiz J, Alvarez Cubero M, Rosado F, Espín E, Bernal C. Confirmed pathogenic effect of a splice site variation in the MLH1 gene causing Lynch syndrome. Int J Colorectal Dis. 2014;29:1019-20 pubmed publisher
  9. Li P, Xiao Z, Braciak T, Ou Q, Chen G, Oduncu F. Systematic immunohistochemical screening for mismatch repair and ERCC1 gene expression from colorectal cancers in China: Clinicopathological characteristics and effects on survival. PLoS ONE. 2017;12:e0181615 pubmed publisher
    ..We also found the determination of ERCC1 expression to be useful for predicting DFS or OS for stage II and III CRC patients. In addition, the expression of MMR genes and ERCC1 showed a significant relationship. ..

More Information


  1. Ma Y, Chen Y, Petersen I. Expression and promoter DNA methylation of MLH1 in colorectal cancer and lung cancer. Pathol Res Pract. 2017;213:333-338 pubmed publisher
    ..MLH1 methylation is a frequent molecular event in CRC and lung cancer patients. In CRC, methylation of MLH1 could be linked to vascular invasiveness. ..
  2. Huang S, Huang S, Chen Y, Chang Y, Chiu Y, Chang I, et al. Overexpression of MutL homolog 1 and MutS homolog 2 proteins have reversed prognostic implications for stage I-II colon cancer patients. Biomed J. 2017;40:39-48 pubmed publisher
    ..1% versus 75.5% (p = 0.024). The reversed prognostic implications in the overexpression of MLH1 and MSH2 for stage I-II colon cancer patients is a novel finding and worthy of further confirmation. ..
  3. Vozdova M, Frohlich J, Kubickova S, Sebestova H, Rubes J. Meiotic Recombination in the Giraffe (G. reticulata). Cytogenet Genome Res. 2017;152:73-80 pubmed publisher
    ..The results are discussed in the context of known data on meiosis in Cetartiodactyla, depicting that the variation in CO frequency among species of this taxonomic group is mostly associated with their diploid chromosome number. ..
  4. Kastrinos F, Uno H, Ukaegbu C, Alvero C, McFarland A, Yurgelun M, et al. Development and Validation of the PREMM5 Model for Comprehensive Risk Assessment of Lynch Syndrome. J Clin Oncol. 2017;35:2165-2172 pubmed publisher
    ..At this threshold, PREMM5 provides performance that is superior to the existing PREMM1,2,6 model in the identification of carriers of LS, including those with weaker phenotypes and individuals unaffected by cancer. ..
  5. Espenschied C, Laduca H, Li S, McFarland R, Gau C, Hampel H. Multigene Panel Testing Provides a New Perspective on Lynch Syndrome. J Clin Oncol. 2017;35:2568-2575 pubmed publisher
    ..These data also highlight the limitations of current testing criteria in identifying these patients, as well as the need for further investigation of cancer risks in patients with MMR mutations. ..
  6. Savio A, Bapat B. Modulation of transcription factor binding and epigenetic regulation of the MLH1 CpG island and shore by polymorphism rs1800734 in colorectal cancer. Epigenetics. 2017;12:441-448 pubmed publisher
    ..These results demonstrate the role of variant rs1800734 in altering transcription factor binding as well as epigenetics at regions beyond the MLH1 CpG island in which it is located. ..
  7. 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
    ..They also illustrate how defective meiotic components can alter the fate of meiotic recombination intermediates, providing new insights for how meiotic recombination pathways are regulated. ..
  8. Dominguez M, Bastos E, Santos E, Oliveira L, Ferreira F, Carraro D, et al. Two new MLH1 germline mutations in Brazilian Lynch syndrome families. Int J Colorectal Dis. 2008;23:1263-4 pubmed publisher
  9. Drost J, van Boxtel R, Blokzijl F, Mizutani T, Sasaki N, Sasselli V, et al. Use of CRISPR-modified human stem cell organoids to study the origin of mutational signatures in cancer. Science. 2017;358:234-238 pubmed publisher
    ..We show that signature 30 can arise from germline NTHL1 mutations. ..
  10. Drage M, Tippayawong M, Agoston A, Zheng Y, Bueno R, Hornick J, et al. Morphological Features and Prognostic Significance of ARID1A-Deficient Esophageal Adenocarcinomas. Arch Pathol Lab Med. 2017;141:970-977 pubmed publisher
    ..Concurrent MLH1 loss is not seen in most ARID1A-deficient tumors, suggesting that ARID1A may be a primary driver of carcinogenesis in a subset of EACs. ..
  11. Savio A, Mrkonjic M, Lemire M, Gallinger S, Knight J, Bapat B. The dynamic DNA methylation landscape of the mutL homolog 1 shore is altered by MLH1-93G>A polymorphism in normal tissues and colorectal cancer. Clin Epigenetics. 2017;9:26 pubmed publisher
  12. Li W, Wang Y, Fang X, Zhou M, Li Y, Dong Y, et al. Differential Expression and Clinical Significance of DNA Methyltransferase 3B (DNMT3B), Phosphatase and Tensin Homolog (PTEN) and Human MutL Homologs 1 (hMLH1) in Endometrial Carcinomas. Med Sci Monit. 2017;23:938-947 pubmed
  13. Stark A, Doukas A, Hugo H, Hedderich J, Hattermann K, Maximilian Mehdorn H, et al. Expression of DNA mismatch repair proteins MLH1, MSH2, and MSH6 in recurrent glioblastoma. Neurol Res. 2015;37:95-105 pubmed publisher
    ..The immunohistochemical expression of MLH1, MSH2, and MSH6 in initial glioblastoma is not associated with patient survival. ..
  14. Boland C, Shike M. Report from the Jerusalem workshop on Lynch syndrome-hereditary nonpolyposis colorectal cancer. Gastroenterology. 2010;138:2197.e1-7 pubmed publisher
  15. Zheng H, Zhou X, Li D, Yang F, Pan H, Li T, et al. Genome-wide alteration in DNA hydroxymethylation in the sperm from bisphenol A-exposed men. PLoS ONE. 2017;12:e0178535 pubmed publisher
    ..Our current study reveals a new mechanism by which BPA exposure reduces human sperm quality. ..
  16. Nagaraju G, Wu C, Merchant N, Chen Z, Lesinski G, El Rayes B. Epigenetic effects of inhibition of heat shock protein 90 (HSP90) in human pancreatic and colon cancer. Cancer Lett. 2017;402:110-116 pubmed publisher
    ..This work demonstrates the effectiveness of ganetespib, an HSP90 inhibitor in modulating DNA methylation through downregulation of DNMT expression. ..
  17. Couch F, Shimelis H, Hu C, Hart S, Polley E, Na J, et al. Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer. JAMA Oncol. 2017;3:1190-1196 pubmed publisher
  18. Pecina Slaus N, Kafka A, Bukovac A, Vladusić T, Tomas D, Hrascan R. Genetic changes of MLH1 and MSH2 genes could explain constant findings on microsatellite instability in intracranial meningioma. Tumour Biol. 2017;39:1010428317705791 pubmed publisher
    ..14; p?=?0.01). Our study contributes to better understanding of the genetic profile of human intracranial meningiomas and suggests that meningiomas harbor defective cellular DNA mismatch repair mechanisms. ..
  19. de la Chapelle A, Palomaki G, Hampel H. Identifying Lynch syndrome. Int J Cancer. 2009;125:1492-3 pubmed publisher
  20. 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
    ..Taken together, our results offer insights into the structure-function relationships of the MutL? complex and reveal unanticipated genetic relationships between components of the meiotic recombination machinery. ..
  21. Hashmi A, Ali R, Hussain Z, Faridi N, Khan E, Bakar S, et al. Mismatch repair deficiency screening in colorectal carcinoma by a four-antibody immunohistochemical panel in Pakistani population and its correlation with histopathological parameters. World J Surg Oncol. 2017;15:116 pubmed publisher
    ..Moreover, right-sided location and intra-tumoral lymphocyte count may be used to identify patients who may need further workup. ..
  22. Carethers J. Differentiating Lynch-like from Lynch syndrome. Gastroenterology. 2014;146:602-4 pubmed publisher
  23. Sciurano R, De Luca G, Rahn I, Solari A. The XY Body of the Cat (Felis catus): Structural Differentiations and Protein Immunolocalization. Cytogenet Genome Res. 2017;152:137-147 pubmed publisher
    ..The sequential changes in the mass and location of SYCP3-containing fibers vary among the clades because of specific processes of axial assembly/disassembly occurring in different species. ..
  24. Pilie P, Johnson A, Hanson K, Dayno M, Kapron A, Stoffel E, et al. Germline genetic variants in men with prostate cancer and one or more additional cancers. Cancer. 2017;123:3925-3932 pubmed publisher
    ..Cancer 2017;123:3925-32. © 2017 American Cancer Society. ..