title: Biochemical DSB-repair model for mammalian cells in G1 and early S phases of the cell cycle.
abstract: The paper presents a model of double strand breaks (DSB) repair in G1 and early S phases of the cell cycle. The model is based on a plethora of published information on biochemical modification of DSB induced by ionizing radiation. So far, three main DSB repair pathways have been identified, including nonhomologous end-joining (NHEJ), homologous recombination (HR), and microhomology-mediated end-joining (MMEJ). During G1 and early S phases of the cell cycle, NHEJ and MMEJ repair pathways are activated dependent on the type of double strand breaks. Simple DSB are a substrate for NHEJ, while complex DSB and DSB in heterochromatin require further end processing. Repair of all DSB start with NHEJ presynaptic processes, and depending on the type of DSB pursue simple ligation, further end processing prior to ligation, or resection. Using law of mass action the model is translated into a mathematical formalism. The solution of the formalism provides the step by step and overall repair kinetics. The overall repair kinetics are compared with the published experimental measurements. Our calculations are in agreement with the experimental results and show that the complex types of DSBs are repaired with slow repair kinetics. The G1 and early S phase model could be employed to predict the kinetics of DSB repair for damage induced by high LET radiation.
authors.affiliation: Radiation Biophysics Group, Department of Oncology-Pathology, Karolinska Institute, Stockholm SE171 76, Sweden. Electronic address: reza.taleei@ki.se.
authors.forename: Reza
authors.initials: R
authors.lastname: Taleei
authors.forename: Hooshang
authors.initials: H
authors.lastname: Nikjoo
mesh_terms: D000818:Animals; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D059766:DNA End-Joining Repair / Q000235:genetics*; D016193:G1 Phase / Q000235:genetics* / Q000528:radiation effects; D008958:Models, Molecular; D011839:Radiation, Ionizing; D059767:Recombinational DNA Repair / Q000235:genetics*; D016196:S Phase / Q000235:genetics* / Q000528:radiation effects
keywords: Biochemical model; DSB repair; Double strand break (DSB)