Modeling the interplay between DNA-PK, Artemis, and ATM in non-homologous end-joining repair in G1 phase of the cell cycle

  • Maryam RouhaniEmail author
Original Paper


Modeling a biological process equips us with more comprehensive insight into the process and a more advantageous experimental design. Non-homologous end joining (NHEJ) is a major double-strand break (DSB) repair pathway that occurs throughout the cell cycle. The objective of the current work is to model the fast and slow phases of NHEJ in G1 phase of the cell cycle following exposure to ionizing radiation (IR). The fast phase contains the major components of NHEJ; Ku70/80 complex, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and XLF/XRCC4/ligase IV complex (XXL). The slow phase in G1 phase of the cell cycle is associated with more complex lesions and involves ATM and Artemis proteins in addition to the major components. Parameters are mainly obtained from experimental data. The model is successful in predicting the kinetics of DSB foci in 13 normal, ATM-deficient, and Artemis-deficient mammalian fibroblast cell lines in G1 phase of the cell cycle after exposure to low doses of IR. The involvement of ATM provides the model with the potency to be connected to different signaling pathways. Ku70/80 concentration and DNA-binding rate as well as XXL concentration and enzymatic activity are introduced as the best targets for affecting NHEJ DSB repair process. On the basis of the current model, decreasing concentration and DNA binding rate of DNA-PKcs is more effective than inhibiting its activity towards the Artemis protein.


Mathematical modeling NHEJ repair ATM Artemis DNA-PKcs 



Ataxia telangiectasia mutated


Correlation coefficient


DNA-dependent protein kinase catalytic subunit


Double-strand break


Homologous recombination


Ionizing radiation


Ku70/80 complex


Mouse embryonic fibroblast


Non-homologous end joining


Phosphatidylinositol 3-kinase-related kinase


XRCC4-like factor


XLF/XRCC4/ligase IV complex



The Institute for Advanced Studies in Basic Sciences (IASBS) is acknowledged for supporting this work.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.


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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Biological SciencesInstitute for Advanced Studies in Basic Sciences (IASBS)ZanjanIran

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