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Paper   IPM / Biological / 16200
School of Biological Sciences
  Title:   A Stochastic Model of DNA Double-Strand Breaks Repair Throughout the Cell Cycle
1.  Fazeleh Mohseni-Salehi
2.  Fatemeh Zare-Mirakabad
3.  Mehdi Sadeghi
4.  Soudeh Ghafouri-Fard
  Status:   Published
  Journal: Bulletin of Mathematical Biology
  No.:  1
  Vol.:  82
  Year:  2021
  Pages:   1-36
  Publisher(s):   Springer US
  Supported by:  IPM
Cell cycle phase is a decisive factor in determining the repair pathway of DNA double-strand breaks (DSBs) by non-homologous end joining (NHEJ) or homologous recombination (HR). Recent experimental studies revealed that 53BP1 and BRCA1 are the key mediators of the DNA damage response (DDR) with antagonizing roles in choosing the appropriate DSB repair pathway in G1, S, and G2 phases. Here, we present a stochastic model of biochemical kinetics involved in detecting and repairing DNA DSBs induced by ionizing radiation during the cell cycle progression. A three-dimensional stochastic process is defined to monitor the cell cycle phase and DSBs repair at times after irradiation. To estimate the model parameters, a Metropolis Monte Carlo method is applied to perform maximum likelihood estimation utilizing the kinetics of γ-H2AX and RAD51 foci formation in G1, S, and G2 phases. The …

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