| Title |
DNA cytosine methyltransferase-directed reactions involving non-cofactor-like compounds / |
| Translation of Title |
DNR citozino metiltransferazių reakcijos, nedalyvaujant kofaktoriui. |
| Authors |
Liutkevičiūtė, Zita |
| Full Text |
|
| Pages |
106 |
| Keywords [eng] |
methyltransferase ; 5-hydroxymethylcytosine ; 5-methylcytosine ; reaction mechanism ; epigenetics |
| Abstract [eng] |
We have shown for the first time that DNA cytosine-5 methyltransferases can perform two atypical reactions in the absence of cofactor in vitro: i) reversible covalent addition of short aliphatic aldehydes to the target cytosine producing 5-(1-hydroxyalkyl)cytosine, and ii) coupling thiols and selenols to 5-hydroxymethylated cytosine residues producing corresponding 5-chalcogenomethylcytosines. These are the first demonstrations of reactions involving non-cofactor-like substrates catalyzed by S-adenosyl-L-methionine dependent enzymes, which reveal atypical versatility of DNA cytosine-5 methyltransferases. Mechanistic insights into of these reactions indicate that the key step in both cases is the covalent activation of the flipped out target residue by the enzyme. It is demonstrated here that the methyltransferase-directed condensation of thiols with 5-hydroxymethylcytosine in DNA can be exploited for covalent labelling of the 5-hydroxymethylcytosine residues permitting subsequent enrichment of corresponding fragments from genomic pools. 5-hydroxymethylcytosine is a recently discovered cytosine modification in mammals whose biological function and distribution are not yet established. |
| Type |
Doctoral thesis |
| Language |
English |
| Publication date |
2012 |
