Ada regulon

Alkyl base lesions can arrest replication, interrupt transcription, or signal the activation of cell cycle checkpoints or apoptosis.

The alkylating agents can introduce methyl or ethyl groups at all of the available nitrogen and oxygen atoms in DNA bases, providing a number of lesions.

The majority of evidence indicates that among the 11 identified base modification two, 3-methyladenine (3meA) and O6-methylguanine (O6-meG), are mainly responsible for the biological effects of alkylation agents.

Intracellular concentrations of σS increase when the cells reach stationary phase; this in turn results in a me-Ada mediated decrease in the expression of AlkA.

[11][12] The 21.7 kDa MGMT protein is built of amino-acid sequences very similar to those of E. coli alkyltransferases, like Ada.

In contrast to the bacterial enzymes it mainly repairs O6meG, whereas removal of the alkyl adduct from O4meT is much slower and significantly less effective.

[13][14] The preferential repair of O6meG is profitable for eukaryotic cells since in experimental animals treated with alkylating carcinogens this lesion is involved in tumor stimulation.

[15][16][17] Crystal structures of AlkB and its human homologue hABH3 have shown similar overall folds, highlighting conserved functional domains.