AID enzymatic activity is inversely proportional to the size of cytosine C5 orbital cloud

PLoS One. 2012;7(8):e43279. doi: 10.1371/journal.pone.0043279. Epub 2012 Aug 20.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytidine Deaminase / metabolism*
  • Cytosine / chemistry
  • Cytosine / metabolism*
  • Deamination
  • Epigenomics
  • Substrate Specificity

Substances

  • Cytosine
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase