Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatic hypermutation (SHM) of Ig genes in B cells is crucial for antibody affinity maturation. The reaction is initiated by cytosine deamination of Ig loci by activation induced deaminase (AID) and is completed by error-prone DNA repair enzyme processing of AID-generated uracils. The mechanisms that target SHM specifically to Ig loci are poorly understood. Recently, it has been demonstrated that although AID preferentially targets Ig loci, it acts surprisingly widely on non-Ig loci, many of which are protected from mutation accumulation by high-fidelity DNA repair. We propose that breakdown of this high fidelity repair process helps explain oncogene mutations observed in B-cell tumors, and further, that many oncogenes are vulnerable to AID-mediated DNA breaks and translocations in normal activated B cells.
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PMID:Balancing AID and DNA repair during somatic hypermutation. 1930 58

DNA methylation is a major epigenetic mechanism for gene silencing. Whereas methyltransferases mediate cytosine methylation, it is less clear how unmethylated regions in mammalian genomes are protected from de novo methylation and whether an active demethylating activity is involved. Here, we show that either knockout or catalytic inactivation of the DNA repair enzyme thymine DNA glycosylase (TDG) leads to embryonic lethality in mice. TDG is necessary for recruiting p300 to retinoic acid (RA)-regulated promoters, protection of CpG islands from hypermethylation, and active demethylation of tissue-specific developmentally and hormonally regulated promoters and enhancers. TDG interacts with the deaminase AID and the damage response protein GADD45a. These findings highlight a dual role for TDG in promoting proper epigenetic states during development and suggest a two-step mechanism for DNA demethylation in mammals, whereby 5-methylcytosine and 5-hydroxymethylcytosine are first deaminated by AID to thymine and 5-hydroxymethyluracil, respectively, followed by TDG-mediated thymine and 5-hydroxymethyluracil excision repair.
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PMID:Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair. 2172 48