Dynamika vybraných proteinů buněčné odpovědi na poškození DNA

Benada, Jan

DNA damage response (DDR) represents a vital signaling network that protects genome integrity and prevents development of cancer. Therefore the study of DDR is of a crucial clinical importance and DDR proteins are promising therapeu- tic targets. Although the great advances have been made mapping out interac- tions between individual DDR proteins, better understanding of complex behav- ior of this network is still needed. One approach, which might help us in this task, is to describe the dynamics of key proteins under different conditions. The first objective of this study was to investigate whether the temporal dynamics of selected DDR proteins differ upon different genotoxic insults, particularly upon γ- irradiation and UV-C irradiation. We showed that under certain insult some DDR proteins exhibit a monotone continuous activation pulse, while the activation of others triggers a series of pulses. We observed a previously described pulsative dynamics of p53 after γ-irradiation in MCF7 cells. Interestingly, we detected a monotone increase of p53 in U2OS after γ-irradiation and similar dynamics upon UV-C irradiation. We suggest that p53 dynamics depends on the presence or ab- sence of effective negative feedback loops between the upstream p53-activating kinases and Wip1 phosphatase. In the second...

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