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

Autoři: Marcin Radom aff001;  Magdalena A. Machnicka aff003;  Joanna Krwawicz aff005;  Janusz M. Bujnicki aff003;  Piotr Formanowicz aff001
Působiště autorů: Institute of Computing Science, Poznan University of Technology, Poznań, Poland aff001;  Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland aff002;  Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, Warsaw, Poland aff003;  Institute of Informatics, University of Warsaw, Warsaw, Poland aff004;  Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland aff005;  Laboratory of Structural Biology, International Institute of Molecular and Cell Biology, Warsaw, Poland aff006;  Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland aff007
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0217913


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.

Klíčová slova:

Biology and life sciences – Genetics – DNA – DNA damage – DNA cleavage – DNA repair – Base excision repair – DNA synthesis – Epigenetics – DNA modification – Gene expression – Biochemistry – Nucleic acids – Biochemical simulations – Cell biology – Chromosome biology – Chromatin – Chromatin modification – DNA methylation – Molecular biology – Molecular biology techniques – Molecular biology assays and analysis techniques – Ligation assay – Computational biology – Research and analysis methods – Chemical synthesis – Biosynthetic techniques – Nucleic acid synthesis


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2019 Číslo 9