[Effects of overexpression of human pol-beta on cellular response to DNA damage].
OBJECTIVE
To investigate the biological effects of overexpression of the human DNA polymerase (pol-beta) on cellular response to DNA damage.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Du
Liu-tao
LT
Department of Health Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
Xu
Lei
L
Yang
Xing-fen
XF
He
Yun
Y
Wei
Qing
Q
Zhuang
Zhi-xiong
ZX
D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D002460:Cell Line; D004249:DNA Damage / Q000235:genetics / Q000502:physiology*; D004252:DNA Mutational Analysis; D019951:DNA Polymerase beta / Q000096:biosynthesis* / Q000235:genetics; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008741:Methyl Methanesulfonate / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity; D009154:Mutation
D009153:Mutagens; D008741:Methyl Methanesulfonate; D019951:DNA Polymerase beta