TY  - CONF
AU  - Popović, Dragan
AU  - Stuchebrukhov, Alexei
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5877
AB  - Damages in DNA structure are often caused by UV light, ionizing radiation, toxic substances and 
environmental pollution. To maintain genetic stability, cells protect themselves against these kinds 
of lesions. Moreover, the main DNA repair processes in prokaryotic and eukaryotic cells are quite 
similar. Photolyases repair the major DNA defects-cyclobutane pyrimidine dimers (CPD) and 
(6-4)-photoproducts. The enzyme contains two photoactive cofactors: folate-the photon antenna 
molecule and catalytically active FADH-form. Photolyase repairs UV (200-300 nm) induced damage in DNA by splitting the ring of CPD dimer into pyrimidine monomers. If not repaired the CPD lesions are highly cytotoxic, mutagenic, and carcinogenic. In the present theoretical/computational study of photolyase from E. coli, continuum electrostatic and electron tunneling currents methods are employed to get a full insight into photoactivation and 
photorepair mechanism of the enzyme and the structure-function interrelation. Protonation state 
of titratable residues, redox potentials of the conserved tryptophan triad, the energetics and kinetic 
reaction rates are calculated comparing well with available experimental data. The free energies of 
all potentially relevant enzyme states during the photoreactivation mechanism are evaluated. This presentation also addresses a several long-time controversial questions about the biological 
relevance of unusual U-shape of FADH cofactor; hopping vs. super-exchange mechanism of the ET pathway; the shortest FADH- to CPD distance, after flipping out the CPD damage to the active site, in the CPD-protein complex or presence of radical FADH* state in the resting state of photolyase. The study could be relevant for other types of photolyases and cryptochromes, which all share the same structural features.
PB  - USA, CA : UC Davis
C3  - 6th Postdoctoral Research Symposium, March 30, 2021, Davis, CA, USA, Web symposium
T1  - DNA Photolyase: Molecular Machinery for Repair of UV-Induced Damage in DNA
SP  - 33
UR  - https://hdl.handle.net/21.15107/rcub_cer_5877
ER  - 

@conference{
author = "Popović, Dragan and Stuchebrukhov, Alexei",
year = "2021",
abstract = "Damages in DNA structure are often caused by UV light, ionizing radiation, toxic substances and 
environmental pollution. To maintain genetic stability, cells protect themselves against these kinds 
of lesions. Moreover, the main DNA repair processes in prokaryotic and eukaryotic cells are quite 
similar. Photolyases repair the major DNA defects-cyclobutane pyrimidine dimers (CPD) and 
(6-4)-photoproducts. The enzyme contains two photoactive cofactors: folate-the photon antenna 
molecule and catalytically active FADH-form. Photolyase repairs UV (200-300 nm) induced damage in DNA by splitting the ring of CPD dimer into pyrimidine monomers. If not repaired the CPD lesions are highly cytotoxic, mutagenic, and carcinogenic. In the present theoretical/computational study of photolyase from E. coli, continuum electrostatic and electron tunneling currents methods are employed to get a full insight into photoactivation and 
photorepair mechanism of the enzyme and the structure-function interrelation. Protonation state 
of titratable residues, redox potentials of the conserved tryptophan triad, the energetics and kinetic 
reaction rates are calculated comparing well with available experimental data. The free energies of 
all potentially relevant enzyme states during the photoreactivation mechanism are evaluated. This presentation also addresses a several long-time controversial questions about the biological 
relevance of unusual U-shape of FADH cofactor; hopping vs. super-exchange mechanism of the ET pathway; the shortest FADH- to CPD distance, after flipping out the CPD damage to the active site, in the CPD-protein complex or presence of radical FADH* state in the resting state of photolyase. The study could be relevant for other types of photolyases and cryptochromes, which all share the same structural features.",
publisher = "USA, CA : UC Davis",
journal = "6th Postdoctoral Research Symposium, March 30, 2021, Davis, CA, USA, Web symposium",
title = "DNA Photolyase: Molecular Machinery for Repair of UV-Induced Damage in DNA",
pages = "33",
url = "https://hdl.handle.net/21.15107/rcub_cer_5877"
}

Popović, D.,& Stuchebrukhov, A.. (2021). DNA Photolyase: Molecular Machinery for Repair of UV-Induced Damage in DNA. in 6th Postdoctoral Research Symposium, March 30, 2021, Davis, CA, USA, Web symposium
USA, CA : UC Davis., 33.
https://hdl.handle.net/21.15107/rcub_cer_5877

Popović D, Stuchebrukhov A. DNA Photolyase: Molecular Machinery for Repair of UV-Induced Damage in DNA. in 6th Postdoctoral Research Symposium, March 30, 2021, Davis, CA, USA, Web symposium. 2021;:33.
https://hdl.handle.net/21.15107/rcub_cer_5877 .

Popović, Dragan, Stuchebrukhov, Alexei, "DNA Photolyase: Molecular Machinery for Repair of UV-Induced Damage in DNA" in 6th Postdoctoral Research Symposium, March 30, 2021, Davis, CA, USA, Web symposium (2021):33,
https://hdl.handle.net/21.15107/rcub_cer_5877 .