Bypass of Methoxyamine-Adducted Abasic Sites by Eukaryotic Translesion DNA Polymerases.

ABSTRACT: The apurinic/apyrimidinic site (AP site) is a highly mutagenic and cytotoxic DNA lesion. Normally, AP sites are removed from DNA by base excision repair (BER). Methoxyamine (MOX), a BER inhibitor currently under clinical trials as a tumor sensitizer, forms adducts with AP sites (AP-MOX) resistant to the key BER enzyme, AP endonuclease. As AP-MOX remains unrepaired, translesion DNA synthesis is expected to be the main mechanism of cellular response to this lesion. However, the mutagenic potential of AP-MOX is still unclear. Here, we compare the blocking and mutagenic properties of AP-MOX and the natural AP site for major eukaryotic DNA polymerases involved in translesion synthesis: DNA polymerases η, ι, ζ, Rev1, and primase-polymerase PrimPol. The miscoding properties of both abasic lesions

SUBMITTER: Yudkina AV 

PROVIDER: S-EPMC11766430 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature