Mouse Anti-MLH1 Recombinant Antibody (CBFYM-2291) (CBMAB-M2476-FY)

Mouse

Human

CBFYM-2291

IgG1, k

IHC-P, WB

Recombinant full length protein (Human)

Human

IgG1, k

Monoclonal

The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Liquid

0.1% Sodium azide

0.1 mg/mL

Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freeze/thaw cycles.

MutL Homolog 1

The protein encoded by this gene can heterodimerize with mismatch repair endonuclease PMS2 to form MutL alpha, part of the DNA mismatch repair system. When MutL alpha is bound by MutS beta and some accessory proteins, the PMS2 subunit of MutL alpha introduces a single-strand break near DNA mismatches, providing an entry point for exonuclease degradation. The encoded protein is also involved in DNA damage signaling and can heterodimerize with DNA mismatch repair protein MLH3 to form MutL gamma, which is involved in meiosis. This gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer.

MutL Homolog 1; COCA2; MutL (E. Coli) Homolog 1 (Colon Cancer, Nonpolyposis Type 2); MutL Homolog 1, Colon Cancer, Nonpolyposis Type 2 (E. Coli); MutL Homolog 1, Colon Cancer, Nonpolyposis Type 2; DNA Mismatch Repair Protein Mlh1

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.

Double-strand break repair via nonhomologous end joining Source: Ensembl
Female meiosis chromosome segregation Source: Ensembl
Homologous chromosome pairing at meiosis Source: Ensembl
Intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
Isotype switching Source: Ensembl
Male meiosis chromosome segregation Source: Ensembl
Meiotic metaphase I plate congression Source: Ensembl
Meiotic spindle midzone assembly Source: Ensembl
Meiotic telomere clustering Source: Ensembl
Mismatch repair Source: MGI
Negative regulation of mitotic recombination Source: Ensembl
Nuclear-transcribed mRNA poly(A) tail shortening Source: Ensembl
Oogenesis Source: Ensembl
Positive regulation of isotype switching to IgA isotypes Source: Ensembl
Positive regulation of isotype switching to IgG isotypes Source: Ensembl
Resolution of meiotic recombination intermediates Source: Ensembl
Response to bacterium Source: Ensembl
Somatic hypermutation of immunoglobulin genes Source: GO_Central
Spermatogenesis Source: Ensembl

Nucleus
Other locations
Chromosome
Note: Recruited to chromatin in a MCM9-dependent manner.

Hereditary non-polyposis colorectal cancer 2 (HNPCC2):
An autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by 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 HNPCC is 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.
Mismatch repair cancer syndrome 1 (MMRCS1):
An autosomal recessive form of mismatch repair cancer syndrome, a childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer.
Muir-Torre syndrome (MRTES):
Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.
Defects in MLH1 may contribute to lobular carcinoma in situ (LCIS), a non-invasive neoplastic disease of the breast.
Endometrial cancer (ENDMC):
A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids.
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 HNPCC but does not have identifiable mutations in MLH1, even though it is silenced, which demonstrates that an epimutation can phenocopy a genetic disease.
Colorectal cancer (CRC);
A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.