FapyG from FapyG:C

FULL NAME: FapyG from FapyG:C


DESCRIPTION:
Treatment of DNA with hydrogen peroxide or other free-redical-generating systems can result in the formation of an imidazole ring-opened derivative of guanine - 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FaPyG). Formamidopyrimidines, 4,6-diamino-5-formamidopyrimidine (FapyAde) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua), are among the major lesions generated in DNA by hydroxyl radical attack, UV radiation, or photosensitization under numerous in vitro and in vivo conditions. They are formed by one-electron reduction of C8-OH-adduct radicals of purines and thus have a common precursor with 8-hydroxypurines generated upon one-electron oxidation. Formamidopyrimidines are repaired by base excision repair (BER). Numerous prokaryotic and eukaryotic DNA glycosylases are highly specific for removal of these lesions from DNA in the first step of this repair pathway, indicating their biological importance. FapyAde and FapyGua are bypassed by DNA polymerases with the insertion of the wrong intact base opposite them, leading to mutagenesis. In mammalian cells, the mutagenicity of FapyGua exceeds that of 8-hydroxyguanine, which is thought to be the most mutagenic of the oxidatively induced lesions in DNA. The background and formation levels of the former in vitro and in vivo equal or exceed those of the latter under various conditions. FapyAde and FapyGua exist in living cells at significant background levels and are abundantly generated upon exposure to oxidative stress. Mice lacking the genes that encode specific DNA glycosylases accumulate these lesions in different organs and, in some cases, exhibit a series of pathological conditions including metabolic syndrome and cancer. Animals exposed to environmental toxins accumulate formamidopyrimidines in their organs.

DAMAGE TYPE: mismatch


DNA DAMAGE SOURCE(S) (MAIN):
reactive oxygen species (ROS)
vinyl chloride metabolites


DNA DAMAGE EFFECT(S) (MAIN):
mutagenesis
point mutation
stalled replication fork
substitution


PATHWAYS:
base excision repair (BER)


DNA repair protein(s) related to damage:
hOGG1


Last modification date: Oct. 8, 2011