Cell cycle phase dependent role of DNA polymerase β in DNA repair and survival after ionizing radiation

PurposeThe purpose of the present study was to determine the role of DNA polymerase β in repair and response after ionizing radiation in different phases of the cell cycle.Methods and materialsSynchronized cells deficient and proficient in DNA polymerase β were irradiated in different phases of the cell cycle as determined by BrdU/flow cytometry. Cell kill and DNA repair were assessed by colony formation and alkaline comet assays, respectively.ResultsWe first demonstrated delayed repair of ionizing radiation induced DNA damage in confluent polymerase β deficient cells. Cell synchronization experiments revealed a cell cycle phase dependence by demonstrating radiation hypersensitivity of polymerase β-deficient cells in G1, but not in the S-phase. Complementing polymerase β-deficient cells with polymerase β reverted the hypersensitivity in G1. Ionizing radiation damage repair was found to be delayed in β-deficient cells when irradiated in G1, but not in S.ConclusionsThe data show a differential role of DNA polymerase β driven base excision and single strand break repair throughout the cell cycle after ionizing radiation damage.