Cytosine
The original nitrogenous base is cytosine, which upon deamination loses its amino group at the C4 position and converts to uracil.
Biochemical Basis of Deamination
Cytosine is a pyrimidine base with a single ring structure that contains an exocyclic amino group. When this amino group is removed through deamination (either spontaneous or enzymatic), the resulting molecule is uracil 1. This conversion is a well-characterized biochemical process that occurs both in normal physiological contexts and as a source of DNA damage 2, 3.
Structural Relationship
- Cytosine structure: Contains an amino group (-NH2) at the C4 position of the pyrimidine ring 4
- Uracil structure: Contains a carbonyl group (=O) at the C4 position instead of the amino group 4
- Single ring: Both cytosine and uracil are pyrimidines, characterized by their six-membered single ring structure, distinguishing them from purines which have double ring structures 4
Biological Significance
The deamination of cytosine to uracil is biologically significant because:
- In DNA: This creates U:G mispairs that are mutagenic, as the original C:G pair becomes U:G, which if unrepaired leads to T:A mutations in subsequent replication 2, 5
- In RNA: Uracil is the normal base, replacing thymine found in DNA 6, 2
- Repair mechanisms: Multiple DNA glycosylases (UNG2, SMUG1, TDG, MBD4) specifically recognize and remove uracil from DNA to prevent mutations 6, 3, 5
Clinical Context
This deamination process has important implications:
- Spontaneous mutations: Cytosine deamination is a major source of spontaneous mutations in cells 2, 3
- Immune system: Enzymatic cytosine deamination by activation-induced deaminase (AID) is essential for antibody diversification in B lymphocytes 3, 5
- Antiviral defense: Host cell enzymes can deaminate cytosine in viral DNA as a defense mechanism against infections including HIV-1 3