Cytotoxic and mutagenic properties of regioisomeric O²-, N3- and O⁴-ethylthymidines in bacterial cells.

ABSTRACT: Exposure to environmental agents and endogenous metabolism can both give rise to DNA alkylation. Thymine is known to be alkylated at O(2), N3 and O(4) positions; however, it remains poorly explored how the regioisomeric alkylated thymidine lesions compromise the flow of genetic information by perturbing DNA replication in cells. Herein, we assessed the differential recognition of the regioisomeric O(2)-, N3- and O(4)-ethylthymidine (O(2)-, N3- and O(4)-EtdT) by the DNA replication machinery of Escherichia coli cells. We found that O(4)-EtdT did not inhibit appreciably DNA replication, whereas O(2)- and N3-EtdT were strongly blocking to DNA replication. In addition, O(4)-EtdT induced a very high frequency of T→C mutation, whereas nucleotide incorporation opposite O(2)- and N3-EtdT was promi

SUBMITTER: Zhai Q 

PROVIDER: S-EPMC4146411 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature