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MLH1

Protein FULL name:

DNA mismatch repair protein Mlh1 isoform 1 [Homo sapiens].


MLH1 (Homo sapiens) is product of expression of MLH1 gene.

Human diseases related to this protein:

MLH1 is involved in:

MMR in Homo sapiens

Keywords:



FUNCTION: Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH6) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS- heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with MLH3 to form MutL gamma which plays a role in meiosis.

SUBUNIT: Heterodimer of MLH1 and PMS2 (MutL alpha), MLH1 and PMS1 (MutL beta) or MLH1 and MLH3 (MutL gamma). Forms a ternary complex with MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50- MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with MBD4. Interacts with EXO1.

INTERACTION: P54278:PMS2; NbExp=1; IntAct=EBI-744248, EBI-1162561; P62328:TMSB4X; NbExp=1; IntAct=EBI-744248, EBI-712598; O75152:ZC3H11A; NbExp=2; IntAct=EBI-744248, EBI-748480;

SUBCELLULAR LOCATION: Nucleus.

TISSUE SPECIFICITY: Colon, lymphocytes, breast, lung, spleen, testis, prostate, thyroid, gall bladder and heart.

DISEASE: Defects in MLH1 are the cause of hereditary non-polyposis colorectal cancer type 2 (HNPCC2) [MIM:609310]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPphenotype (also called Lynch syndrome). Most families with clinically recognized HNPhave mutations in either MLH1 or MSH2 genes. HNPis an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPis reported to be the most common form of inherited colorectal cancer in the Western world, and accounts for 15% of all colon cancers. Cancers in HNPoriginate within benign neoplastic polyps termed adenomas. Clinically, HNPis often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPis based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected.

DISEASE: Defects in MLH1 are a cause of mismatch repair cancer syndrome (MMRCS) [MIM:276300]; also known as Turcot syndrome or brain tumor-polyposis syndrome 1 (BTPS1). MMRCS is an autosomal dominant disorder characterized by malignant tumors of the brain associated with multiple colorectal adenomas. Skin features include sebaceous cysts, hyperpigmented and cafe au lait spots.

DISEASE: Defects in MLH1 are a cause of Muir-Torre syndrome (MTS) [MIM:158320]. MTS is a rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.

DISEASE: Note=Defects in MLH1 may contribute to lobular carcinoma in situ (LCIS), a non-invasive neoplastic disease of the breast.

DISEASE: Defects in MLH1 are a cause of susceptibility to endometrial cancer [MIM:608089].

DISEASE: Note=Some epigenetic changes can be transmitted unchanged through the germline (termed 'epigenetic inheritance'). Evidence that this mechanism occurs in humans is provided by the identification of individuals in whom 1 allele of the MLH1 gene is epigenetically silenced throughout the soma (implying a germline event). These individuals are affected by HNPbut does not have identifiable mutations in MLH1, even though it is silenced, which demonstrates that an epimutation can phenocopy a genetic disease.

SIMILARITY: Belongs to the DNA mismatch repair mutL/hexB family.

WEB RESOURCE: Name=Hereditary non-polyposis colorectal cancer db; [LINK]

WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; [LINK]

WEB RESOURCE: Name=GeneReviews; [LINK]

WEB RESOURCE: Name=NIEHS-SNPs; [LINK]


This protein can be a part of a given complexes:
NCBI GenPept GI number(s): 4557757
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot P40692 P40692
PFAM: - P40692 (Link - using uniprot id)
InterPro: - P40692 (Link - using uniprot id)
CATH: None  
SCOP: None  
PDB: - -


Protein sequence:
MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVI
VKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFR
GEALASISHVAHVTITTKTADGKCAYRASYSDGKLKAPPKPCAGNQGTQI
TVEDLFYNIATRRKALKNPSEEYGKILEVVGRYSVHNAGISFSVKKQGET
VADVRTLPNASTVDNIRSIFGNAVSRELIEIGCEDKTLAFKMNGYISNAN
YSVKKCIFLLFINHRLVESTSLRKAIETVYAAYLPKNTHPFLYLSLEISP
QNVDVNVHPTKHEVHFLHEESILERVQQHIESKLLGSNSSRMYFTQTLLP
GLAGPSGEMVKSTTSLTSSSTSGSSDKVYAHQMVRTDSREQKLDAFLQPL
SKPLSSQPQAIVTEDKTDISSGRARQQDEEMLELPAPAEVAAKNQSLEGD
TTKGTSEMSEKRGPTSSNPRKRHREDSDVEMVEDDSRKEMTAACTPRRRI
INLTSVLSLQEEINEQGHEVLREMLHNHSFVGCVNPQWALAQHQTKLYLL
NTTKLSEELFYQILIYDFANFGVLRLSEPAPLFDLAMLALDSPESGWTEE
DGPKEGLAEYIVEFLKKKAEMLADYFSLEIDEEGNLIGLPLLIDNYVPPL
EGLPIFILRLATEVNWDEEKECFESLSKECAMFYSIRKQYISEESTLSGQ
QSEVPGSIPNSWKWTVEHIVYKALRSHILPPKHFTEDGNILQLANLPDLY
KVFERC

MLH1 (Homo sapiens) is able to recognize following damages:
MLH1 (Homo sapiens) belongs to following protein families:
References:

Title Authors Journal
Endonucleolytic function of MutLalpha in human mismatch repair. Kadyrov FA, Dzantiev L, Constantin N, Modrich P
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Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Bronner CE, Baker SM, Morrison PT, Warren G, Smith LG, Lescoe MK, Kane M, Earabino C, Lipford J, Lindblom A, et al. Nature March 17, 1994
Mutation of a mutL homolog in hereditary colon cancer. Papadopoulos N, Nicolaides NC, Wei YF, Ruben SM, Carter KC, Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM, Adams MD, et al. Science March 18, 1994
Genomic structure of human mismatch repair gene, hMLH1, and its mutation analysis in patients with hereditary non-polyposis colorectal cancer (HNPCC) Han HJ, Maruyama M, Baba S, Park JG, Nakamura Y Hum Mol Genet Jan. 1, 1995
Structure of the human MLH1 locus and analysis of a large hereditary nonpolyposis colorectal carcinoma kindred for mlh1 mutations. Kolodner RD, Hall NR, Lipford J, Kane MF, Morrison PT, Finan PJ, Burn J, Chapman P, Earabino C, Merchant E, et al. Cancer Res Feb. 15, 1995
The molecular basis of Turcot's syndrome. Hamilton SR, Liu B, Parsons RE, Papadopoulos N, Jen J, Powell SM, Krush AJ, Berk T, Cohen Z, Tetu B, et al. N Engl J Med March 1, 1995
Majority of hMLH1 mutations responsible for hereditary nonpolyposis colorectal cancer cluster at the exonic region 15-16. Wijnen J, Khan PM, Vasen H, Menko F, van der Klift H, van den Broek M, van Leeuwen-Cornelisse I, Nagengast F, Meijers-Heijboer EJ, Lindhout D, Griffioen G, Cats A, Kleibeuker J, Varesco L, Bertario L, Bisgaard ML, Mohr J, Kolodner R, Fodde R Am J Hum Genet Jan. 1, 1996
CpG dinucleotides in the hMSH2 and hMLH1 genes are hotspots for HNPCC mutations. Maliaka YK, Chudina AP, Belev NF, Alday P, Bochkov NP, Buerstedde JM Hum Genet Jan. 1, 1996
Mutational analysis of mismatch repair genes, hMLH1 and hMSH2, in sporadic endometrial carcinomas with microsatellite instability. Kobayashi K, Matsushima M, Koi S, Saito H, Sagae S, Kudo R, Nakamura Y Jpn J Cancer Res Jan. 1, 1996
The genetic basis of Muir-Torre syndrome includes the hMLH1 locus. Bapat B, Xia L, Madlensky L, Mitri A, Tonin P, Narod SA, Gallinger S Am J Hum Genet Sept. 1, 1996
Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in patients with sporadic, familial and hereditary colorectal cancer. Moslein G, Tester DJ, Lindor NM, Honchel R, Cunningham JM, French AJ, Halling KC, Schwab M, Goretzki P, Thibodeau SN Hum Mol Genet Sept. 1, 1996
Germline mutations of hMLH1 and hMSH2 genes in Korean hereditary nonpolyposis colorectal cancer. Han HJ, Yuan Y, Ku JL, Oh JH, Won YJ, Kang KJ, Kim KY, Kim S, Kim CY, Kim JP, Oh NG, Lee KH, Choe KJ, Nakamura Y, Park JG J Natl Cancer Inst Sept. 18, 1996
Use of SSCP analysis to identify germline mutations in HNPCC families fulfilling the Amsterdam criteria. Beck NE, Tomlinson IP, Homfray T, Frayling I, Hodgson SV, Harocopos C, Bodmer WF Hum Genet Jan. 1, 1997
Mutational analysis of the hMLH1 gene using an automated two-dimensional DNA typing system. Sasaki S, Tokino T, Miyatsu T, Muto T, Nakamura Y Hum Mutat Jan. 1, 1997
Molecular basis of HNPCC: mutations of MMR genes. Papadopoulos N, Lindblom A Hum Mutat Jan. 1, 1997
Hereditary nonpolyposis colorectal cancer (HNPCC): eight novel germline mutations in hMSH2 or hMLH1 genes. Wehner M, Buschhausen L, Lamberti C, Kruse R, Caspari R, Propping P, Friedl W Hum Mutat Jan. 1, 1997
Characterization of MSH2 and MLH1 mutations in Italian families with hereditary nonpolyposis colorectal cancer. Viel A, Genuardi M, Capozzi E, Leonardi F, Bellacosa A, Paravatou-Petsotas M, Pomponi MG, Fornasarig M, Percesepe A, Roncucci L, Tamassia MG, Benatti P, Ponz de Leon M, Valenti A, Covino M, Anti M, Foletto M, Boiocchi M, Neri G Genes Chromosomes Cancer Feb. 1, 1997
Germline HNPCC gene variants have little influence on the risk for sporadic colorectal cancer. Tomlinson IP, Beck NE, Homfray T, Harocopos CJ, Bodmer WF J Med Genet Feb. 1, 1997
MSH2 and MLH1 mutations in sporadic replication error-positive colorectal carcinoma as assessed by two-dimensional DNA electrophoresis. Wu Y, Nystrom-Lahti M, Osinga J, Looman MW, Peltomaki P, Aaltonen LA, de la Chapelle A, Hofstra RM, Buys CH Genes Chromosomes Cancer April 1, 1997
Mean age of tumor onset in hereditary nonpolyposis colorectal cancer (HNPCC) families correlates with the presence of mutations in DNA mismatch repair genes. Pensotti V, Radice P, Presciuttini S, Calistri D, Gazzoli I, Grimalt Perez A, Mondini P, Buonsanti G, Sala P, Rossetti C, Ranzani GN, Bertario L, Pierotti MA Genes Chromosomes Cancer July 1, 1997
Hereditary nonpolyposis colorectal cancer families not complying with the Amsterdam criteria show extremely low frequency of mismatch-repair-gene mutations. Wijnen J, Khan PM, Vasen H, van der Klift H, Mulder A, van Leeuwen-Cornelisse I, Bakker B, Losekoot M, Moller P, Fodde R Am J Hum Genet Aug. 1, 1997
Hereditary nonpolyposis colorectal cancer: causative role of a germline missense mutation in the hMLH1 gene confirmed by the independent occurrence of the same somatic mutation in tumour tissue. Wang Y, Friedl W, Lamberti C, Ruelfs C, Kruse R, Propping P Hum Genet Sept. 1, 1997
A human compound heterozygote for two MLH1 missense mutations. Hackman P, Tannergard P, Osei-Mensa S, Chen J, Kane MF, Kolodner R, Lambert B, Hellgren D, Lindblom A Nat Genet Oct. 1, 1997
Germline hMSH2 and hMLH1 gene mutations in incomplete HNPCC families. Wang Q, Desseigne F, Lasset C, Saurin JC, Navarro C, Yagci T, Keser I, Bagci H, Luleci G, Gelen T, Chayvialle JA, Puisieux A, Ozturk M Int J Cancer Dec. 10, 1997
DGGE screening of mutations in mismatch repair genes (hMSH2 and hMLH1) in 34 Swedish families with colorectal cancer. Liu T, Wahlberg S, Rubio C, Holmberg E, Gronberg H, Lindblom A Clin Genet Jan. 1, 1998
A novel missense mutation in the DNA mismatch repair gene hMLH1 present among East Asians but not among Europeans. Wang Y, Friedl W, Lamberti C, Nothen MM, Kruse R, Propping P Hum Hered Jan. 1, 1998
Four new mutations in the DNA mismatch repair gene MLH1 in colorectal cancers with microsatellite instability. Mutations in brief no. 157. Online. Klaus K, Herfarth F, Ogunbiyi OA, Moley JF, Kodner IJ, Wells SA Jr, Goodfellow PJ Hum Mutat Jan. 1, 1998
hMLH1 mutations in hereditary nonpolyposis colorectal cancer kindreds. Mutations in brief no. 182. Online. Panariello L, Scarano MI, de Rosa M, Capasso L, Renda A, Riegler G, Rossi GB, Salvatore F, Izzo P Hum Mutat Jan. 1, 1998
Hereditary nonpolyposis coloretal cancer: identification of novel germline mutations in two kindreds not fulfulling the Amsterdam criteria. Mutations in brief no. 203. Online. Quaresima B, Grandinetti C, Baudi F, Tassone P, Barbieri V, Conforti S, Avvedimento EV, Costanzo F, Venuta S Hum Mutat Jan. 1, 1998
Germline mutations of hMLH1 and hMSH2 genes in patients with suspected hereditary nonpolyposis colorectal cancer and sporadic early-onset colorectal cancer. Yuan Y, Han HJ, Zheng S, Park JG Dis Colon Rectum April 1, 1998
Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and controls. Farrington SM, Lin-Goerke J, Ling J, Wang Y, Burczak JD, Robbins DJ, Dunlop MG Am J Hum Genet Sept. 1, 1998
Excess of hMLH1 germline mutations in Swiss families with hereditary non-polyposis colorectal cancer. Hutter P, Couturier A, Membrez V, Joris F, Sappino AP, Chappuis PO Int J Cancer Dec. 9, 1998
Assessment of pathogenicity criteria for constitutional missense mutations of the hereditary nonpolyposis colorectal cancer genes MLH1 and MSH2. Genuardi M, Carrara S, Anti M, Ponz de Leon M, Viel A Eur J Hum Genet Jan. 1, 1999
Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in 75 French kindreds with nonpolyposis colorectal cancer. Wang Q, Lasset C, Desseigne F, Saurin JC, Maugard C, Navarro C, Ruano E, Descos L, Trillet-Lenoir V, Bosset JF, Puisieux A Hum Genet Jan. 1, 1999
Novel hMLH1 and hMSH2 germline mutations in African Americans with colorectal cancer. Weber TK, Chin HM, Rodriguez-Bigas M, Keitz B, Gilligan R, O'Malley L, Urf E, Diba N, Pazik J, Petrelli NJ JAMA Jan. 1, 1999
Neurofibromatosis and early onset of cancers in hMLH1-deficient children. Wang Q, Lasset C, Desseigne F, Frappaz D, Bergeron C, Navarro C, Ruano E, Puisieux A Cancer Res Feb. 15, 1999
MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1. Bellacosa A, Cicchillitti L, Schepis F, Riccio A, Yeung AT, Matsumoto Y, Golemis EA, Genuardi M, Neri G Proc Natl Acad Sci U S A March 1, 1999
Microsatellite instability-a useful diagnostic tool to select patients at high risk for hereditary non-polyposis colorectal cancer: a study in different groups of patients with colorectal cancer. Lamberti C, Kruse R, Ruelfs C, Caspari R, Wang Y, Jungck M, Mathiak M, Malayeri HR, Friedl W, Sauerbruch T, Propping P Gut June 1, 1999
Influence of selection criteria on mutation detection in patients with hereditary nonpolyposis colorectal cancer. Heinimann K, Scott RJ, Buerstedde JM, Weber W, Siebold K, Attenhofer M, Muller H, Dobbie Z Cancer June 15, 1999
Frequent microsatellite instability and mismatch repair gene mutations in young Chinese patients with colorectal cancer. Chan TL, Yuen ST, Chung LP, Ho JW, Kwan KY, Chan AS, Ho JC, Leung SY, Wyllie AH J Natl Cancer Inst July 21, 1999
Missense mutations in hMLH1 associated with colorectal cancer. Liu T, Tannergard P, Hackman P, Rubio C, Kressner U, Lindmark G, Hellgren D, Lambert B, Lindblom A Hum Genet Nov. 1, 1999
Detection of mutations in mismatch repair genes in Portuguese families with hereditary non-polyposis colorectal cancer (HNPCC) by a multi-method approach. Fidalgo P, Almeida MR, West S, Gaspar C, Maia L, Wijnen J, Albuquerque C, Curtis A, Cravo M, Fodde R, Leitao CN, Burn J Eur J Hum Genet Feb. 1, 2000
Enhanced detection of deleterious and other germline mutations of hMSH2 and hMLH1 in Japanese hereditary nonpolyposis colorectal cancer kindreds. Nomura S, Sugano K, Kashiwabara H, Taniguchi T, Fukayama N, Fujita S, Akasu T, Moriya Y, Ohhigashi S, Kakizoe T, Sekiya T Biochem Biophys Res Commun April 1, 2000
BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J Genes Dev April 15, 2000
Mutational germline analysis of hMSH2 and hMLH1 genes in early onset colorectal cancer patients. Montera M, Resta N, Simone C, Guanti G, Marchese C, Civitelli S, Mancini A, Pozzi S, De Salvo L, Bruzzone D, Donadini A, Romio L, Mareni C J Med Genet July 1, 2000
hMLH1 and hMSH2 mutations in families with familial clustering of gastric cancer and hereditary non-polyposis colorectal cancer. Kim JC, Kim HC, Roh SA, Koo KH, Lee DH, Yu CS, Lee JH, Kim TW, Lee HL, Beck NE, Bodmer WF Cancer Detect Prev Jan. 1, 2001
Optimization of experimental conditions for RNA-based sequencing of MLH1 and MSH2 genes. Jakubowska A, Gorski B, Kurzawski G, Debniak T, Hadaczek P, Cybulski C, Kladny J, Oszurek O, Scott RJ, Lubinski J Hum Mutat Jan. 1, 2001
Extensive somatic microsatellite mutations in normal human tissue. Vilkki S, Tsao JL, Loukola A, Poyhonen M, Vierimaa O, Herva R, Aaltonen LA, Shibata D Cancer Res June 1, 2001
HNPCC mutations in the human DNA mismatch repair gene hMLH1 influence assembly of hMutLalpha and hMLH1-hEXO1 complexes. Jager AC, Rasmussen M, Bisgaard HC, Singh KK, Nielsen FC, Rasmussen LJ Oncogene June 14, 2001
Contribution of germline MLH1 and MSH2 mutations to lobular carcinoma in situ of the breast. Stone JG, Coleman G, Gusterson B, Marossy A, Lakhani SR, Ward A, Nash A, McKinna A, A'Hern R, Stratton MR, Houlston RS Cancer Lett June 26, 2001
The interaction of DNA mismatch repair proteins with human exonuclease I. Schmutte C, Sadoff MM, Shim KS, Acharya S, Fishel R J Biol Chem Aug. 31, 2001
Functional analysis of human MLH1 and MSH2 missense variants and hybrid human-yeast MLH1 proteins in Saccharomyces cerevisiae. Ellison AR, Lofing J, Bitter GA Hum Mol Genet Sept. 1, 2001
Sixteen rare sequence variants of the hMLH1 and hMSH2 genes found in a cohort of 254 suspected HNPCC (hereditary non-polyposis colorectal cancer) patients: mutations or polymorphisms? Muller-Koch Y, Kopp R, Lohse P, Baretton G, Stoetzer A, Aust D, Daum J, Kerker B, Gross M, Dietmeier W, Holinski-Feder E Eur J Med Res Nov. 20, 2001
Eight novel germline MLH1 and MSH2 mutations in hereditary non-polyposis colorectal cancer families from Spain. Godino J, de La Hoya M, Diaz-Rubio E, Benito M, Caldes T Hum Mutat Dec. 1, 2001
Functional analysis of MLH1 mutations linked to hereditary nonpolyposis colon cancer. Nystrom-Lahti M, Perrera C, Raschle M, Panyushkina-Seiler E, Marra G, Curci A, Quaresima B, Costanzo F, D'Urso M, Venuta S, Jiricny J Genes Chromosomes Cancer Jan. 1, 2002
Functional analysis of hMLH1 variants and HNPCC-related mutations using a human expression system. Trojan J, Zeuzem S, Randolph A, Hemmerle C, Brieger A, Raedle J, Plotz G, Jiricny J, Marra G Gastroenterology Feb. 1, 2002
Seven novel MLH1 and MSH2 germline mutations in hereditary nonpolyposis colorectal cancer. Kruger S, Plaschke J, Pistorius S, Jeske B, Haas S, Kramer H, Hinterseher I, Bier A, Kreuz FR, Theissig F, Saeger HD, Schackert HK Hum Mutat Feb. 1, 2002
Pathogenicity of missense and splice site mutations in hMSH2 and hMLH1 mismatch repair genes: implications for genetic testing. Cravo M, Afonso AJ, Lage P, Albuquerque C, Maia L, Lacerda C, Fidalgo P, Chaves P, Cruz C, Nobre-Leitao C Gut March 1, 2002
Mutations of hMLH1 and hMSH2 in patients with suspected hereditary nonpolyposis colorectal cancer: correlation with microsatellite instability and abnormalities of mismatch repair protein expression. Scartozzi M, Bianchi F, Rosati S, Galizia E, Antolini A, Loretelli C, Piga A, Bearzi I, Cellerino R, Porfiri E J Clin Oncol March 1, 2002
Microsatellite instability and mutation analysis of candidate genes in unselected sardinian patients with endometrial carcinoma. Baldinu P, Cossu A, Manca A, Satta MP, Pisano M, Casula M, Dessole S, Pintus A, Tanda F, Palmieri G Cancer June 15, 2002
hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer. Rossi BM, Lopes A, Oliveira Ferreira F, Nakagawa WT, Napoli Ferreira CC, Casali Da Rocha JC, Simpson CC, Simpson AJ Ann Surg Oncol July 1, 2002
Impact of microsatellite testing and mismatch repair protein expression on the clinical interpretation of genetic testing in hereditary non-polyposis colorectal cancer. Ward R, Meldrum C, Williams R, Mokany E, Scott R, Turner J, Hawkins N, Burgess B, Groombridge C, Spigelman A J Cancer Res Clin Oncol Aug. 1, 2002
Germline MSH2 and MLH1 mutational spectrum in HNPCC families from Poland and the Baltic States. Kurzawski G, Suchy J, Kladny J, Safranow K, Jakubowska A, Elsakov P, Kucinskas V, Gardovski J, Irmejs A, Sibul H, Huzarski T, Byrski T, Debniak T, Cybulski C, Gronwald J, Oszurek O, Clark J, Gozdz S, Niepsuj S, Slomski R, Plawski A, Lacka-Wojciechowska A, Rozmiarek A, Fiszer-Maliszewska L, Bebenek M, Sorokin D, Stawicka M, Godlewski D, Richter P, Brozek I, Wysocka B, Jawien A, Banaszkiewicz Z, Kowalczyk J, Czudowska D, Goretzki PE, Moeslein G, Lubinski J J Med Genet Oct. 1, 2002
Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected by a novel mutation detection approach. Gille JJ, Hogervorst FB, Pals G, Wijnen JT, van Schooten RJ, Dommering CJ, Meijer GA, Craanen ME, Nederlof PM, de Jong D, McElgunn CJ, Schouten JP, Menko FH Br J Cancer Oct. 7, 2002
Functional alterations of human exonuclease 1 mutants identified in atypical hereditary nonpolyposis colorectal cancer syndrome. Sun X, Zheng L, Shen B Cancer Res Nov. 1, 2002
Identification of six novel MSH2 and MLH1 germline mutations in HNPCC. Kruger S, Plaschke J, Jeske B, Gorgens H, Pistorius SR, Bier A, Kreuz FR, Theissig F, Aust DE, Saeger HD, Schackert HK Hum Mutat April 1, 2003
Genetic analysis of familial colorectal cancer in Israeli Arabs. Chen-Shtoyerman R, Theodor L, Harmati E, Friedman E, Dacka S, Kopelman Y, Sternberg A, Zarivach R, Bar-Meir S, Fireman Z Hum Mutat April 1, 2003
Molecular analysis of hereditary nonpolyposis colorectal cancer in the United States: high mutation detection rate among clinically selected families and characterization of an American founder genomic deletion of the MSH2 gene. Wagner A, Barrows A, Wijnen JT, van der Klift H, Franken PF, Verkuijlen P, Nakagawa H, Geugien M, Jaghmohan-Changur S, Breukel C, Meijers-Heijboer H, Morreau H, van Puijenbroek M, Burn J, Coronel S, Kinarski Y, Okimoto R, Watson P, Lynch JF, de la Chapelle A, Lynch HT, Fodde R Am J Hum Genet May 1, 2003
Microsatellite instability and mutation analysis among southern Italian patients with colorectal carcinoma: detection of different alterations accounting for MLH1 and MSH2 inactivation in familial cases. Colombino M, Cossu A, Arba A, Manca A, Curci A, Avallone A, Comella G, Botti G, Scintu F, Amoruso M, D'Abbicco D, d'Agnessa MR, Spanu A, Tanda F, Palmieri G Ann Oncol Oct. 1, 2003
Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non-polyposis colorectal cancer: identification of novel and recurrent deletions by MLPA. Taylor CF, Charlton RS, Burn J, Sheridan E, Taylor GR Hum Mutat Dec. 1, 2003
Characterization of human exonuclease 1 in complex with mismatch repair proteins, subcellular localization and association with PCNA. Nielsen FC, Jager AC, Lutzen A, Bundgaard JR, Rasmussen LJ Oncogene Jan. 19, 2004
Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double primary cancers of the colorectum and the endometrium: a population-based study in northern Sweden. Cederquist K, Emanuelsson M, Goransson I, Holinski-Feder E, Muller-Koch Y, Golovleva I, Gronberg H Int J Cancer April 10, 2004
Germline epimutation of MLH1 in individuals with multiple cancers. Suter CM, Martin DI, Ward RL Nat Genet May 1, 2004
HNPCC mutation MLH1 P648S makes the functional protein unstable, and homozygosity predisposes to mild neurofibromatosis type 1. Raevaara TE, Gerdes AM, Lonnqvist KE, Tybjaerg-Hansen A, Abdel-Rahman WM, Kariola R, Peltomaki P, Nystrom-Lahti M Genes Chromosomes Cancer July 1, 2004
The MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer. Lipkin SM, Rozek LS, Rennert G, Yang W, Chen PC, Hacia J, Hunt N, Shin B, Fodor S, Kokoris M, Greenson JK, Fearon E, Lynch H, Collins F, Gruber SB Nat Genet July 1, 2004
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J Genome Res Oct. 1, 2004
Germline mutations in MLH1, MSH2 and MSH6 in Korean hereditary non-polyposis colorectal cancer families. Shin YK, Heo SC, Shin JH, Hong SH, Ku JL, Yoo BC, Kim IJ, Park JG Hum Mutat Oct. 1, 2004
Ten novel MSH2 and MLH1 germline mutations in families with HNPCC. Kruger S, Bier A, Plaschke J, Hohl R, Aust DE, Kreuz FR, Pistorius SR, Saeger HD, Rothhammer V, Al-Taie O, Schackert HK Hum Mutat Oct. 1, 2004
Functional significance and clinical phenotype of nontruncating mismatch repair variants of MLH1. Raevaara TE, Korhonen MK, Lohi H, Hampel H, Lynch E, Lonnqvist KE, Holinski-Feder E, Sutter C, McKinnon W, Duraisamy S, Gerdes AM, Peltomaki P, Kohonen-Ccorish M, Mangold E, Macrae F, Greenblatt M, de la Chapelle A, Nystrom M Gastroenterology Aug. 1, 2005
Human mismatch repair: reconstitution of a nick-directed bidirectional reaction. Constantin N, Dzantiev L, Kadyrov FA, Modrich P J Biol Chem Dec. 2, 2005
Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study). Kurzawski G, Suchy J, Lener M, Klujszo-Grabowska E, Kladny J, Safranow K, Jakubowska K, Jakubowska A, Huzarski T, Byrski T, Debniak T, Cybulski C, Gronwald J, Oszurek O, Oszutowska D, Kowalska E, Gozdz S, Niepsuj S, Slomski R, Plawski A, Lacka-Wojciechowska A, Rozmiarek A, Fiszer-Maliszewska L, Bebenek M, Sorokin D, Sasiadek MM, Stembalska A, Grzebieniak Z, Kilar E, Stawicka M, Godlewski D, Richter P, Brozek I, Wysocka B, Limon J, Jawien A, Banaszkiewicz Z, Janiszewska H, Kowalczyk J, Czudowska D, Scott RJ, Lubinski J Clin Genet Feb. 1, 2006
MutLalpha: at the cutting edge of mismatch repair. Jiricny J Cell July 28, 2006
Inheritance of a cancer-associated MLH1 germ-line epimutation. Hitchins MP, Wong JJ, Suthers G, Suter CM, Martin DI, Hawkins NJ, Ward RL N Engl J Med Jan. 15, 2007
Functional analysis of human MLH1 variants using yeast and in vitro mismatch repair assays. Takahashi M, Shimodaira H, Andreutti-Zaugg C, Iggo R, Kolodner RD, Ishioka C Cancer Res May 15, 2007
Biallelic germline mutations of mismatch-repair genes: a possible cause for multiple pediatric malignancies. Poley JW, Wagner A, Hoogmans MM, Menko FH, Tops C, Kros JM, Reddingius RE, Meijers-Heijboer H, Kuipers EJ, Dinjens WN Cancer June 1, 2007
Mechanisms and functions of DNA mismatch repair Guo-Min Li Cell Res. Jan. 18, 2008
Direct visualization of asymmetric adenine-nucleotide-induced conformational changes in MutL alpha. Sacho EJ, Kadyrov FA, Modrich P, Kunkel TA, Erie DA Mol Cell Feb. 18, 2008
Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancer. Barnetson RA, Cartwright N, van Vliet A, Haq N, Drew K, Farrington S, Williams N, Warner J, Campbell H, Porteous ME, Dunlop MG Hum Mutat March 1, 2008
A quantitative atlas of mitotic phosphorylation. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP Proc Natl Acad Sci U S A Aug. 5, 2008
A large fraction of unclassified variants of the mismatch repair genes MLH1 and MSH2 is associated with splicing defects. Tournier I, Vezain M, Martins A, Charbonnier F, Baert-Desurmont S, Olschwang S, Wang Q, Buisine MP, Soret J, Tazi J, Frebourg T, Tosi M Hum Mutat Dec. 1, 2008
Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK Sci Signal Jan. 1, 2009


Last modification of this entry: Nov. 11, 2010.

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