Vertebrate POLQ and POLβ cooperate in base excision repair of oxidative DNA damage

Base excision repair (BER) plays an essential role in protecting cells from mutagenic base damage caused by oxidative stress, hydrolysis, and environmental factors. POLO is a DNA polymerase, which appears to be involved in translesion DNA synthesis (TLS) past base damage. We disrupted POLO, and its homologs HEL308 and POLN in chicken DT40 cells, and also created polq/hel308 and polq/poln double mutants. We found that POLQ-deficient mutants exhibit hypersensitivity to oxidative base damage induced by H2O2, but not to UV or cisplatin. Surprisingly, this phenotype was synergistically increased by concomitant deletion of the major BER polymerase, POLO. Moreover, extracts from a polq null mutant cell line show reduced BER activity, and POLO, like POLO, accumulated rapidly at sites of base damage. Accordingly, POLO and POLO share an overlapping function in the repair of oxidative base damage. Taken together, these results suggest a role for vertebrate POLO in BER.