DNA methyltransferase

Function

DNA methyltransferase (DNMT) catalyzes the transfer of methyl group to DNA. Methylation is essential for gene expression. DNMT uses S-adenosyl methionine (SAM) as the methyl donor. The SAM analog S-adenosyl homocysteine (SAH) is a powerful inhibitor of DNMT.

  • Methylguanine DNMT repairs the DNA lesion O6-methylguanine to guanine.[1]
  • Methylcytosine DNMT methylates the 5 position of cytosine. [2]
  • Methyladenine DNMT methylates the 6 position of adenine. [3]
  • HhaI DNA methyltransferase (HDMT), a DNMT from Haemophilus haemolyticus recognizes the 5’-GCGC-3’ DNA sequence and methylates the first cytosine to convert it to 5-methylcytosine. The SAM serves as the methyl donor in the reaction and is converted to to S-adenosyl-L-homocysteine (SAH) by the reaction[4].

Relevance

DNMT inhibitors are being tested in cancer therapy.

Disease

The human ICF disorder is caused by mutations in DNMT 3B.

Structural highlights

The .

3D Structures of DNA methyltransferase

DNA methyltransferase 3D structures


Adenine DNMT complex with SAM and Cl- ion (PDB code 1nw5).

Drag the structure with the mouse to rotate

ReferencesReferences

  1. Kaina B, Christmann M, Naumann S, Roos WP. MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents. DNA Repair (Amst). 2007 Aug 1;6(8):1079-99. Epub 2007 May 7. PMID:17485253 doi:http://dx.doi.org/10.1016/j.dnarep.2007.03.008
  2. Kumar S, Cheng X, Klimasauskas S, Mi S, Posfai J, Roberts RJ, Wilson GG. The DNA (cytosine-5) methyltransferases. Nucleic Acids Res. 1994 Jan 11;22(1):1-10. PMID:8127644
  3. Thomas CB, Scavetta RD, Gumport RI, Churchill ME. Structures of liganded and unliganded RsrI N6-adenine DNA methyltransferase: a distinct orientation for active cofactor binding. J Biol Chem. 2003 Jul 11;278(28):26094-101. Epub 2003 May 4. PMID:12732637 doi:http://dx.doi.org/10.1074/jbc.M303751200
  4. Sankpal UT, Rao DN. Structure, function, and mechanism of HhaI DNA methyltransferases. Crit Rev Biochem Mol Biol. 2002;37(3):167-97. PMID:12139442 doi:http://dx.doi.org/10.1080/10409230290771492

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky