Petri net–based model of the human DNA base excision repair pathway

by Marcin Radom, Magdalena A. Machnicka, Joanna Krwawicz, Janusz M. Bujnicki, Piotr Formanowicz

Cellular DNA is daily exposed to several damaging agents causing a plethora of DNA lesions. As a first aid to restore DNA integrity, several enzymes got specialized in damage recognition and lesion removal during the process called base excision repair (BER). A large number of DNA damage types and several different readers of nucleic acids lesions during BER pathway as well as two sub-pathways were considered in the definition of a model using the Petri net framework. The intuitive graphical representation in combination with precise mathematical analysis methods are the strong advantages of the Petri net-based representation of biological processes and make Petri nets a promising approach for modeling and analysis of human BER. The reported results provide new information that will aid efforts to characterize in silico knockouts as well as help to predict the sensitivity of the cell with inactivated repair proteins to different types of DNA damage. The results can also help in identifying the by-passing pathways that may lead to lack of pronounced phenotypes associated with mutations in some of the proteins. This knowledge is very useful when DNA damage-inducing drugs are introduced for cancer therapy, and lack of DNA repair is desirable for tumor cell death.