Coupling of cell fate selection model enhances DNA damage response and may underlie BE phenomenon

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Demirkiran G., Demir G., Guzelis C.

IET SYSTEMS BIOLOGY, cilt.14, sa.2, ss.96-106, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 14 Sayı: 2
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1049/iet-syb.2019.0081
  • Dergi Adı: IET SYSTEMS BIOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, Compendex, Computer & Applied Sciences, EMBASE, INSPEC, MEDLINE
  • Sayfa Sayıları: ss.96-106
  • Anahtar Kelimeler: biological effects of ionising particles, molecular biophysics, biochemistry, DNA, cellular biophysics, physiological models, biomolecular effects of radiation, cellular effects of radiation, biological effects of X-rays, oscillations, proteins, three-mode two-dimensional oscillators, p53-mediated cell fate selection, globally coupled DSB-induced cells, coupled model consists, coupling mechanism, ATM variable, bystander signal, intercellular medium, sensitive DNA damage response, coupled p53 network oscillators, intercellular coupling, cell fate selection model, double-strand break-induced cells, DSBs, neighbour cells, oscillatory response, excitatory coupling, plausible coupling model, DOUBLE-STRAND BREAKS, DOSE HYPER-RADIOSENSITIVITY, BYSTANDER RESPONSE, CIRCADIAN CLOCKS, NITRIC-OXIDE, RADIATION, P53, COMMUNICATION, REPAIR, INITIATION
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Double-strand break-induced (DSB) cells send signal that induces DSBs in neighbour cells, resulting in the interaction among cells sharing the same medium. Since p53 network gives oscillatory response to DSBs, such interaction among cells could be modelled as an excitatory coupling of p53 network oscillators. This study proposes a plausible coupling model of three-mode two-dimensional oscillators, which models the p53-mediated cell fate selection in globally coupled DSB-induced cells. The coupled model consists of ATM and Wip1 proteins as variables. The coupling mechanism is realised through ATM variable via a mean-field modelling the bystander signal in the intercellular medium. Investigation of the model reveals that the coupling generates more sensitive DNA damage response by affecting cell fate selection. Additionally, the authors search for the cause-effect relationship between coupled p53 network oscillators and bystander effect (BE) endpoints. For this, they search for the possible values of uncertain parameters that may replicate BE experiments' results. At certain parametric regions, there is a correlation between the outcomes of cell fate and endpoints of BE, suggesting that the intercellular coupling of p53 network may manifest itself as the form of observed BEs.