|Application ||WB, IHC, ICC, E|
|Description||DNA-mismatch repair (MMR), a conserved process that involves correcting errors made during DNA synthesis, is crucial to the maintenance of genomic integrity. Lack of a functional DNA-mismatch repair pathway is a commoncharacteristic of several different types of human cancers, either due to anMMR gene mutation or promoter-methylation gene silencing. MLH1 is a human homolog of the E. coli DNA mismatch repair gene mutL, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in hereditary nonpolyposis colon cancer (HNPCC). MLH1 is an integralpart of the protein complex responsible for mismatch repair expressed inlymphocytes, heart, colon, breast, lung, spleen, testis, prostate, thyroid andgall bladder, and is methylated in several ovarian tumors. Loss of MLH1 protein expression is associated with a mutated phenotype, microsatellite instability and a predisposition to cancer. In hereditary nonpolyposis colorectalcancer (HNPCC), an autosomal dominant inherited cancer syndrome that signifies a high risk of colorectal and various other types of cancer, the MLH1 gene exhibits a pathogenic mutation. Inactivation of the MLH1 gene causes genome instability and predisposition to cancer. MLH1 also plays a role in meiotic recombination.|
|Immunogen||Purified recombinant fragment of MLH1 (aa381-483) expressed in E. Coli. |
|Formulation||Ascitic fluid containing 0.03% sodium azide.|
|Other Names||DNA mismatch repair protein Mlh1, MutL protein homolog 1, MLH1, COCA2|
|Dilution||WB~~1/500 - 1/2000|
IHC~~1/200 - 1/1000
IF~~1/200 - 1/1000
|Storage||Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C in small aliquots to prevent freeze-thaw cycles.|
|Precautions||MLH1 Antibody is for research use only and not for use in diagnostic or therapeutic procedures.|
|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-MSH3) 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.|
|Tissue Location||Colon, lymphocytes, breast, lung, spleen, testis, prostate, thyroid, gall bladder and heart|
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