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Theoretical Modelling of Catalytic Mechanism of the DNA Repair Enzymes


Project Description

Serious sequel to organism may occur due to the corrupted function of nucleic acids upon their damage. The repair of damaged DNA operated by the base-excision repair enzymes (BER enzymes) is closely related to autonomous therapeutic pathways that ensure basal chemical processes in cell. The discovery of BER was recently awarded by the Nobel price. Although several BER enzymes targeting particular damages of DNA were described up to date, their catalytic mechanisms remained largely unknown. Our recent study on the function of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) BER enzyme highlighted new facts concerning the catalytic excision of 8-oxo-2′-deoxyguanosine (8-oxo-G) that arises due to damage of normal guanosine. 8-oxo-G is one of the most frequently occurring and dangerous lesions due to the oxidative damage to DNA that can occur normally within respiratory pathways in cell and upon unwanted chemicals. The PhD project will be focused on theoretical research of hOGG1 and other BER enzymes by employing the methods of theoretical chemistry such as QM, QM/MM and MD for calculations of physicochemical properties of DNA-BER enzyme complex including NMR spectroscopic parameters. The theoretical calculations will be used for interpretation of experiments conducted in Czech and Japanese laboratories.

How to apply

To apply for a PhD study at IOCB Prague, you must hold a Master’s degree (MSc) or the equivalent of the MSc in similar field (four or five year undergraduate degree). The application can be submitted before obtaining the Master’s degree, however, the applicant should obtain the degree within five months after the application deadline.

For more information visit our website “Call for PhD applications 2019”:
https://www.uochb.cz/web/structure/797.html

You can apply online via our application form http://www.uochb.cz/phdapplication/index.php/PhDrecruitment

Enquiries

All general enquiries should be directed to Katerina Solcova (). Scientific enquiries can be addressed to the supervisor ().

Funding Notes

Regular monthly income of students at IOCB Prague varies depending on the faculty scholarship and supervisor's financial options.

References

1. Šebera, J., et al. Pyramidalization of the Glycosidic Nitrogen Provides the Way for Efficient Cleavage of the N-Glycosidic Bond of 8-OxoG with the hOGG1 DNA Repair Protein, Journal of Physical Chemistry B, 116, (2012), pp 12535-12544.
2. Šebera, J., et al. The mechanism of the glycosylase reaction with hOGG1 base-excision repair enzyme: concerted effect of Lys249 and Asp268 during excision of 8-oxoguanine”, Nucleic Acids Res., 45, (2017), pp 5231-5242.

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