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

Abstract Purpose The 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 materials Synchronized 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. Results We 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. Conclusions The 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.