Mechanisms of DNA damage and repair (2309)

Title doc.dr. Sc Davor Zahradka, senior zn. associate
the doc.dr.sc. Ksenia Zahradka, higher zn. Associate

Ruđer Boskovic Institute

Learn the different forms of DNA molecule damage and molecular mechanisms of their repair to preserve the genetic integrity and viability of each cell and organism.

The subject will give an overview of the different types of damage in the DNA molecule, the factors that provoke them, and the molecular mechanisms involved in their repair. Dna repair mechanisms in prokaryotes and eukaryotes will be compared. Special emphasis will be placed on genes, enzymes and molecular processes related to recombinational DNA repair. Thematic units will be as follows:
1) FACTORS that damage DNA: external (ionizing radiation, UV radiation, chemical agents) and internal (damage caused during DNA replication, oxidative DNA damage, spontaneous loss of bases);
2) types of DNA damage: wrongly paired bases, apurine and apirimidine (AP) sites, altered bases, single-stranded fractures, double-stranded fractures, cross-linking chains;
3) DNA repair mechanisms: damage reversion (e.g. photoreactivation), excision repair, recombination repair (homologous and non-chromologic recombination), repair of wrongly paired bases;
4) cellular agreement on DNA damage (pr. SOS response in bacteria);
5) molecular mechanisms of diseases caused by disorders in DNA repair.

1. To analyse the factors (endogenous and exogenous) that damage the DNA molecule and the types of DNA molecule damage.
2. Examine molecular mechanisms for repairing DNA damage.
3. Describe the main mechanisms of radiation resistance on the example of Deinococcus radiodurans.
4. Predict molecular mechanisms of diseases caused by dna repair disorders.
5. Assess the importance of DNA repair to maintain cell viability and avoid disease development.

regular attendance, seminar work

If there are material possibilities, we are ready to organize practical work in the laboratory.

Friedberg, E.C., Walker, G.C., Siede, W. 1995 DNA Repair and Mutagenesis, American Society for Microbiology, Washington, D.C. (selected chapters)
Iyer, R.. R., Pluciennik, A., Burdett, V., Modrich, P.L. DNA mismatch repair: functions and mechanisms. Chem. Rev. 2006, 106:302-23.
Kemp, M.G. Sancar, A. DNA excision repair: Where do all the dimers go? Cell Cycle 2012, 11:2997-3002.
Michel, B., Leach, D. Homologous Recombination – Enzymes and Pathways. EcoSal Plus 2013; doi:10.1128/ecosalplus.7.2.7.
Mimitou, E.P., Symington, L.S. Nucleases and helicases take center stage in homologous recombination. Trends. The biochem. Sci. 2009, 34:264-72.
Wallace, S.S. Base excision repair: A critical player in many games. DNA Repair 2014, 7:14-26 p.m.
Weterings, E., Chen, D.J. The endless tale of non-homologous end-joining. Cell Res. 2008, 18: 114-24.

Defais, M., Devoret, R. SOS response. In Encyclopedia of Life Sciences. 2001, Nature Publishing Group, www.els.net
Sedgwick, B. Repairing DNA-methylation damage. Nat. Rev. Breakwater. The cell. Biol. 2004, 5:148-57.
Kowalczykowski, S.C. Initiation of genetic recombination and recombination-dependent replication. Trends. The biochem. Sci. 2000, 25:156-65.
Kreuzer, K.N. Interplay between DNA replication and recombination in prokaryotes. Anna. Rev. Microbiol. 2005, 59:43-67.
Michel, B., Grompone, G., Flores, M.-J., Bidnenko, V. Multiple pathways process stalled replication forks. Proc. Natl. The Acad. Sci. USA 101:12783-88.
San Filippo, J., Sung, P., Klein, H. Mechanism of eukaryotic homologous recombination. Anna. Rev. The biochem. 2008, 77:229-57.
De Boer, J., Hoeijmakers, J.H.J. Nucleotide excision repair and human syndromes. Carcinogenesis 2000, 9:453-60 p.m.
Shuck, S.C., Short, E.A., Turchi, J.J. Eukaryotic nucleotide excision repair: from understanding mechanism to influencing biology. Cell Res. 2008, 18:64-72.
Yi, C., He, C. DNA repair by reversal of DNA damage. Cold Spring Harb. Perspect. Biol. 2013; 5:a012575
Prakash, R., Zhang, Y., Feng, W., Jasin, M. Homologous recombination and human health. The roles of BRCA1, BRCA2, and associated proteins. Cold Spring Harb. Perspect. Biol. 2015; 7:a016600
Radman, M. Mismatch repair earns Nobel Prize in Chemistry 2015 to Paul Modrich for a biochemical tour de force. DNA Repair 2016, 37:A22-8.

- checking the understanding of information for individual lectures
- discussions with students
- questionnaire on case performance performance
- the success of the course will be evaluated annually by the joint expert committee of the Rudjer Boskovic Institute, the University of Dubrovnik and the University of Osijek