Abstract
The absolute and relative pool sizes of deoxyribonucleotides (dRNs) are essential in DNA replication fidelity, DNA damage and repair. We found in this study that although DNA damage induced by methyl methanesulfonate (MMS) seemed similar in cancer (HepG2) and normal (LO2) cells, more extensive alterations in ribonucleotides (RNs) and dRNs pools occurred in HepG2 cells indicating that HepG2 cells were more vigilant to DNA damage. After 10 h repair, RNs pools were still severely perturbed in LO2 cells. Compared to LO2 cells, deoxyribonucleotide triphosphates (dNTPs) pools in HepG2 cells elevated by more folds which could facilitate more efficient DNA repair and improve survival probability following DNA damage, although this should definitely lead to higher mutation rates. DNA repair was more efficient in HepG2 cells at S phase and it partly came to an end while DNA repair was still uncompleted in LO2 cells outside S phase. In conclusion, our results demonstrated that HepG2 and LO2 cells presented many differences in nucleotide metabolism, cell cycle checkpoints and DNA repair pathways in response to DNA damage, which could be potential targets for cancer treatment.
Highlights
The integrity and stability of DNA are essential to each cell because DNA is the repository of genetic information, which is stored as a code consisted of deoxyribonucleotide triphosphates
We found in this study that DNA damage induced by methyl methanesulfonate (MMS) seemed similar in cancer (HepG2) and normal (LO2) cells, more extensive alterations in ribonucleotides (RNs) and dRNs pools occurred in HepG2 cells indicating that HepG2 cells were more vigilant to DNA damage
Studies conducted in yeasts and mammalian cells report that imbalance of endogenous deoxyribonucleotide triphosphates (dNTPs) pools can lead to DNA damage, inhibition of DNA replication fork progression, cell-cycle arrest, growth retardation, high mutation rates, and carcinogenesis via several interrelated mechanisms [8, 12, 13]
Summary
The integrity and stability of DNA are essential to each cell because DNA is the repository of genetic information, which is stored as a code consisted of deoxyribonucleotide triphosphates (dNTPs). The free dNTPs used in DNA synthesis are more susceptible to damage than are bases in duplex DNA [3]. To cope with these DNA damages, cells have developed a complex network of DNA repair mechanisms [1, 4]. A variety of different DNA repair pathways have been reported including direct reversal, base excision repair, nucleotide excision repair, mismatch repair, and recombination repair pathways. In these pathways, cells require extra amounts of dNTPs to repair DNA. Manipulating DNA damage and repair has potential to sensitize cells to these therapies
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