Structural and functional characterization of proteins and protein domains involved in DNA repair and maintenance of genome integrity.

Acronim: DNAtraffic

Funding - 405 660 PLN


The main role of DNA molecules is the long-term storage of information – genetic instruction used in the development and functioning of all known living organisms. Cells are continuously exposed to the endogenous damaging agents and the environmental factors such as chemicals, UV light, ionizing radiation which are known as the DNA damaging factors (mutagens). Unrepaired lesions might be the result of dysfunction in DNA repair, and lead to aging, carcinogenesis or neurodegeneration. Some pathological disorders are directly related to defects in DNA repair machinery. The knowledge of the DNA repair pathways is critical to our understanding of how and why the genome is affected during the lifespan of the organism, and how the DNA repair systems efficiently work via several different pathways to protect the genome from potential mutagenic modification and allow accurate transmission of genetic information.

The DNAtraffic Project is a research focused on structural and functional characterization of DNA damage and DNA repair proteins in order to annotate their function in nucleic acids repair pathways.

Planned Results:
DNA repair is a very complicated process, involving many factors in human cells. Particularly, we will focus on proteins involved in the nucleic acids repair and/or modification. We plan to study the role of AlkB human homologues (ALKBH2 and ALKBH3) towards their recognition, binding and removal in a direct manner of the mutagen-induced lesions. However, many of the proteins involved in DNA metabolism are very well described (including substrate specificity, kinetics, mechanisms of action) but information about different factors involved in DNA repair are scattered in the literature. Moreover, there are still processes, for which an enzymatic activity is known or suspected to exist, but the proteins have not been characterized yet. We plan to organize information on nucleic acid metabolism at the systems level and further develop our earlier established database, namely the DNAtraffic database.

We believe that our study will allow us to annotate functions to still uncharacterized proteins and/or protein domains involved in maintenance of genome integrity.

Target Group:
The character of the project is strictly scientific, however its influence on medical science and human health can’t be excluded in ulterior time.