Methylated-DNA-protein-cysteine methyltransferase is an enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 that in humans is encoded by the MGMT gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

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Function

O(6)-alkyl-guanine

Guanine

Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...

 is the major carcinogenic lesion in DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 induced by alkylating

Alkylation

Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene . Alkylating agents are widely used in chemistry because the alkyl group is probably the most common group encountered in...

 mutagen

Mutagen

In genetics, a mutagen is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level. As many mutations cause cancer, mutagens are therefore also likely to be carcinogens...

s. This DNA adduct

DNA adduct

In molecular genetics, a DNA adduct is a piece of DNA covalently bonded to a chemical. This process could be the start of a cancerous cell, or carcinogenesis. DNA adducts in scientific experiments are used as biomarkers of exposure and as such are themselves measured to reflect quantitatively,...

 is removed by the repair protein, O(6)-methylguanine-DNA methyltransferase. This protein is not a true enzyme since it accepts the alkyl group from the lesion in a stoichiometric

Stoichiometry

Stoichiometry is a branch of chemistry that deals with the relative quantities of reactants and products in chemical reactions. In a balanced chemical reaction, the relations among quantities of reactants and products typically form a ratio of whole numbers...

 reaction and the active enzyme is not regenerated after it is alkylated. The methyl-acceptor residue in the protein is cysteine

Cysteine

Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

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Clinical significance

Methylation

DNA methylation

DNA methylation is a biochemical process that is important for normal development in higher organisms. It involves the addition of a methyl group to the 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring...

 of the gene's promoter may play a significant role in carcinogenesis

Carcinogenesis

Carcinogenesis or oncogenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells...

. In patients with glioblastoma multiforme

Glioblastoma multiforme

Glioblastoma multiforme is the most common and most aggressive malignant primary brain tumor in humans, involving glial cells and accounting for 52% of all functional tissue brain tumor cases and 20% of all intracranial tumors. Despite being the most prevalent form of primary brain tumor, GBMs...

, a severe type of brain tumor, the methylation state of the MGMT gene determined whether tumor cells would be responsive to temozolomide

Temozolomide

Temozolomide Temozolomide Temozolomide (brand names Temodar and Temodal is an oral alkylating agent which can be used for the treatment of Grade IV astrocytoma — an aggressive brain tumor, also known as glioblastoma multiforme as well as melanoma, a form of skin cancer...

; if the promotor was methylated, temozolomide was more effective.

MGMT has also been shown to be a useful tool increasing gene therapy efficiency. By using a two component vector consisting of a transgene of interest and MGMT, in vivo drug selection can be utalized to select for successfully transduced cells.

Interactions

O-6-methylguanine-DNA methyltransferase has been shown to interact

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with estrogen receptor alpha

Estrogen receptor alpha

Estrogen receptor alpha , also known as NR3A1 , is a nuclear receptor that is activated by the sex hormone estrogen...

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Further reading