Polymerase β Limits the Rate of DNA Single-Strand Break Repair
Pozdnyakov E.M., Korneichuk A.D., Rogacheva A.V., Vasilev G.A.
Moscow State University M.V. Lomonosov, Moscow, Russia
Abstract. Breaks that appear in DNA and violate its integrity are a serious threat to the life of the cell. There is a special repair system for their recovery, which includes many different enzymes. However, the exact mechanisms of this process are currently still unclear. In this article, we considered single-strand discontinuities based on the Michaelis–Menten equation and using the quasi-equilibrium approximation. A scheme of interaction between the mechanisms of the reparation system was developed and a computational model was built in the COPASI software to verify it. As a result of the work, the dependences of the concentrations of the participants in the repair system were obtained, and the known experimental data were also approximated. We observed that the plot with a logarithmic scale of fully corrected DNA concentration versus time is close to a sigmoid. We obtained that, the polymerase enzymatic reaction is the limiting factor for the rate of DNA repair and the rate of ligase operation is limited by the rate of DNA appearance. Being a regulatory link in the DNA repair system, polymerase and its parameters exert a control influence on the rest of the model parameters. In turn, the parameters for PARP1, PNKP, and LIG3α should provide rates of enzymatic reactions higher than the rate of polymerase operation.
Key words: DNA repair, Michaelis–Menten kinetics, single strand break, base excision repair, POLbeta, model.