Divergent evolution of opposite base specificity and single-stranded DNA activity in animal and plant AP endonucleases.

ABSTRACT: Apurinic/apyrimidinic (AP) endonucleases are key enzymes responsible for the repair of base-less nucleotides generated by spontaneous hydrolysis or as DNA repair intermediates. APE1, the major human AP endonuclease, is a druggable target in cancer and its biological function has been extensively studied. However, the molecular features responsible for its substrate specificity are poorly understood. We show here that, in contrast to APE1, its Arabidopsis ortholog ARP (apurinic endonuclease-redox protein) exhibits orphan base-dependent activity on double-stranded DNA and very poor AP cleavage capacity on single-stranded DNA (ssDNA). We found that these differences are largely a consequence of the variation at two DNA intercalating amino acids that have undergone divergent changes in the met

SUBMITTER: Jordano-Raya M 

PROVIDER: S-EPMC11707538 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature