Impact of ribonucleotide incorporation by DNA polymerases ? and ? on oxidative base excision repair.

ABSTRACT: Oxidative stress is a very frequent source of DNA damage. Many cellular DNA polymerases (Pols) can incorporate ribonucleotides (rNMPs) during DNA synthesis. However, whether oxidative stress-triggered DNA repair synthesis contributes to genomic rNMPs incorporation is so far not fully understood. Human specialized Pols ? and ? are the important enzymes involved in the oxidative stress tolerance, acting both in base excision repair and in translesion synthesis past the very frequent oxidative lesion 7,8-dihydro-8-oxoguanine (8-oxo-G). We found that Pol ?, to a greater extent than Pol ? can incorporate rNMPs opposite normal bases or 8-oxo-G, and with a different fidelity. Further, the incorporation of rNMPs opposite 8-oxo-G delays repair by DNA glycosylases. Studies in Pol ?- and ?-deficient cell extracts suggest that Pol ? levels can greatly affect rNMP incorporation opposite oxidative DNA lesions.

SUBMITTER: Crespan E 

PROVIDER: S-EPMC4773436 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature