3-methyl C (3meC)

FULL NAME: 3-methylcytosine


DESCRIPTION:
N3-methylcytosine (3MeC) is formed by SN2 agents such as MMS and the naturally occurring methyl halides preferentially in single-stranded DNA. It has been detected both in vitro and in vivo. 3MeC stalls DNA synthesis and is likely to be toxic. In E.coli, the AlkB protein has good activity against 3MeC and 3EtC both in vitro and in vivo. The appreciable mutagenesis and toxicity of the 3-alkylcytosines in vivo is decimated by AlkB, although a portion of the toxicity can also be overcome by induction of the SOS bypass polymerases. With regard to mutagenic potential, if a cell has no AlkB and uninduced SOS bypass polymerases, 3MeC and 3EtC are 30% mutagenic, with the predominant mutations being C → T and C → A. Basal expression of AlkB of a few molecules per cell abrogates the mutagenicity of 3MeC and 3EtC, whereas expression of SOS bypass polymerases in the absence of AlkB increases the mutagenicity of both lesions to a striking 70%. Although investigations involving replication past 1MeA and 1MeG, which similarly have a blocked Watson–Crick hydrogen bonding face, by DNA polymerases in vitro are lacking, it is known from in vitro studies that 3MeC inhibits replication by DNA polymerase I and does not cause mutation. However, some adduct bypass occurs with the incorporation of dAMP and dTMP opposite 3MeC. Therefore, the rules for misreplication of the 3-alkylcytosine lesions are the same both in vitro and in vivo, although the replicative system in cells is capable of a much higher mutation rate than is achieved in vitro.

DAMAGE TYPE: methylation damage


DNA DAMAGE SOURCE(S) (MAIN):
SN2 methylating agents
methyl methanesulfonate (MMS)
methyl chloride
methyl bromide
methyl iodide
alkylating agents


DNA DAMAGE EFFECT(S) (MAIN):
cytotoxic
stalled replication fork


DNA DAMAGE EFFECT(S) (MINOR):
C→A transversion
C→T transition
mutagenesis
point mutation
substitution
transition
transversion


PATHWAYS:
base excision repair (BER)
direct reversal (DR)


DNA repair protein(s) related to damage:
AlkB
ALKBH2
ALKBH3
ANPG (MPG)


Last modification date: Oct. 15, 2011