Abstract
To investigate DNA damage response in the model crenarchaeon Sulfolobus islandicus, four different DNA damage agents were tested for their effects on cell death of this archaeon, including UV irradiation, methyl methanesulfonate, cisplatin, and 4-nitroquinoline 1-oxide (NQO). Cell death featured with DNA-less cell formation was revealed in DNA damage treatment with each agent. Cellular responses upon NQO treatment were characterized in details, and following sequential events were revealed, including: a modest accumulation of G1/S phase cells, membrane depolarization, proteolytic degradation of chromatin proteins, and chromosomal DNA degradation. Further insights into the process were gained from studying drugs that affect the archaeal ATP synthase, including a proton gradient uncoupler and an ATP synthase inhibitor. Whereas the proton uncoupler-mediated excess proton influx yielded cell death as observed for the NQO treatment, inhibition of ATP synthase attenuated NQO-induced membrane depolarization and DNA-less cell formation. In conclusion, the NQO-induced cell death in S. islandicus is characterized by proteolytic degradation of chromatin protein, and chromosomal DNA degradation, which probably represents a common feature for the cell death induced by different DNA damage agents.
Highlights
All living organisms encounter various endogenous factors and environmental stimuli that damage their genetic material, yielding DNA lesions that should be repaired properly in order to maintain their genome integrity
The results showed that all these DNA damage agents killed most cells in treated cultures (≥99.9%) at a lethal dosage, which were 400 J/m2 of UV irradiation, 4 μM nitroquinoline 1-oxide (NQO), 2.6 mM methyl methanesulfonate (MMS) and 20 mg/L cisplatin, respectively (Supplementary Figure 1)
We analyzed the levels of Cren7 and Sul7 in the UV, MMS- and cisplatin-treated cells, and the results indicated that chromatin protein degradation occurred during each DNA damage treatment at a lethal dose (Supplementary Figure 4)
Summary
All living organisms encounter various endogenous factors and environmental stimuli that damage their genetic material, yielding DNA lesions that should be repaired properly in order to maintain their genome integrity. Investigation of DNA lesion repair in bacteria and eukaryotes has revealed that these DNA repair activities are under the control of a signal transduction pathway named DNA damage response (DDR). Mechanisms of DNA-Less Cell Formation in Sulfolobus function in cell cycle arrest or diverse DNA repair pathways, and cell cycle only resumes after the completion of DNA damage repair (Giglia-Mari et al, 2011; Maréchal and Zou, 2013; Baharoglu and Mazel, 2014). Cell death is induced if the extent of DNA damage is beyond the repair capacity of the cell. Metazoans employ programmed cell death to eliminate cells containing a severely damaged genome in order to maintain the genome stability at the organismal level and avoid cancerogenesis (Elmore, 2007)
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