Distinct Roles of Ape1 Protein, An Enzyme Involved in DNA Repair, in High or Low Linear Energy Transfer Ionizing Radiation-induced Cell Killing [DNA and Chromosomes]

September 10th, 2014 by Wang, H., Wang, X., Chen, G., Zhang, X., Tang, X., Park, D., Cucinotta, F. A., Yu, D. S., Deng, X., Dynan, W. S., Doetsch, P. W., Wang, Y.

High linear energy transfer (LET) radiation from space heavy charged particles or a heavier ion radiotherapy machine kills more cells than low-LET radiation, mainly because high-LET radiation-induced DNA damage is more difficult to repair. Relative biological effectiveness (RBE) is the ratio of the effects generated by high-LET radiation to low-LET radiation. Previously, our group and others demonstrated that the cell killing RBE is involved in the interference of high-LET radiation with non-homologous end-joining (NHEJ) but not homologous recombination repair (1-4). This effect is attributable, in part, to the small DNA fragments (< 40 bp) directly produced by high-LET radiation, the size of which prevents Ku protein from efficiently binding to the two ends of one fragment at the same time, thereby reducing NHEJ efficiency (3,5). Here we demonstrate that Ape1, an enzyme required for processing apurinic/apyrimidinic (AP, known as abasic) sites, is also involved in the generation of small DNA fragments during the repair of high-LET radiation-induced base damage, which contributes to the higher RBE of high-LET in cell killing. This discovery opens a new direction to develop approaches for either protecting astronauts from exposure to space radiation or benefiting cancer patients by sensitizing tumor cells to high-LET radiotherapy.
  • Posted in Journal of Biological Chemistry, Publications
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