AID enzymatic activity is inversely proportional to the size of cytosine C5 orbital cloud.
Activation induced deaminase (AID) deaminates cytosine to uracil, which is required for a functional humoral immune system. Previous work demonstrated, that AID also deaminates 5-methylcytosine (5 mC). Recently, a novel vertebrate modification (5-hydroxymethylcytosine - 5 hmC) has been implicated in functioning in epigenetic reprogramming, yet no molecular pathway explaining the removal of 5 hmC has been identified. AID has been suggested to deaminate 5 hmC, with the 5 hmU product being repaired by base excision repair pathways back to cytosine. Here we demonstrate that AID's enzymatic activity is inversely proportional to the electron cloud size of C5-cytosine - H > F > methyl >> hydroxymethyl. This makes AID an unlikely candidate to be part of 5 hmC removal.
DNA Editing in Immunity and Epigenetics, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy.
Gopinath
G
Rangam
Kerstin-Maike
KM
Schmitz
Alexander J A
AJ
Cobb
Svend K
SK
Petersen-Mahrt
D000818:Animals; D003564:Cytidine Deaminase / Q000378:metabolism*; D003596:Cytosine / Q000737:chemistry / Q000378:metabolism*; D003641:Deamination; D057890:Epigenomics; D013379:Substrate Specificity; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D003596:Cytosine; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase