Effects of overexpression of human pol-β on cellular response to DNA damage

Abstract

To investigate the biological effects of overexpression of the human DNA polymerase (pol-beta) on cellular response to DNA damage. The cell strain HLFbeta from the stable overexpression of the human pol-beta was contaminated with methyl methanesulfonate (MMS) for investigating the effects of the pol-beta on the cellular responses to DNA damage on the aspects such as the DNA damage, the cell cycle and the induced mutation rate. The cell HLFbeta from the stable overexpression of the human pol-beta was obtained through the screening. The cellular response to DNA damage of HLFbeta induced by the MMS in the intermediate and high dosage group (ranging from 0.5 to 0.8 mmol/L) was significantly lower than that in the control group. The analysis for the cell cycle distribution showed that both the two types of cells contaminated by MMS had retardation at G(2) phase. In the HLFbeta group, the cells had the obvious G(2) phase retardation and 49.0% of the cells were retarded at G(1) phase as well when the MMS was increased to 0.5 mmol/L while in the control, only 20.1% of the cells were retarded at the G(1) phase when the same dosage of MMS was administered. Moreover, the MMS-induced mutagenesis in HLFbeta was increased from 4.5 x 10(-6) to 8.2 x 10(-6), significantly higher than that in the control group (P < 0.05). High Pol-beta level decreases cellular DNA damage induced by MMS. Nevertheless, the overexpression of Pol-beta can also increase error-prone DNA synthesis during DNA repair process.