Error-free replicative bypass of thymine glycol by the combined action of DNA polymerases kappa and zeta in human cells.

ABSTRACT: Thymine glycol (Tg) is the most common DNA lesion of thymine induced by interaction with reactive oxygen species. Because of the addition of hydroxyl groups at C5 and C6 in a Tg lesion, the damaged base loses its aromatic character and becomes nonplanar; consequently, the C5 methyl group protrudes in an axial direction and that prevents the stacking of the 5' base above the Tg lesion. Because Tg presents a severe block to continued synthesis by replicative DNA polymerases, we determine here how human cells manage to replicate through this lesion. Using a duplex plasmid system where bidirectional replication ensues from an origin of replication, we show that translesion synthesis (TLS) makes a prominent contribution to Tg bypass and that it occurs in a predominantly error-free fashion. Also

SUBMITTER: Yoon JH 

PROVIDER: S-EPMC2922520 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature