How Does Dna Repair Enzyme Photolyase Prevent Skin Cancer
Skin cancer is the most common form of cancer in the United States and can be lethal if non properly treated. The leading cause of skin cancer is epidermal absorption of ultraviolet (UV) radiation. Dna is believed to be the primary chromophore. Indeed, photochemical reactions involving DNA have been linked to mutagenesis, carcinogenesis and cell death. Fortunately, nature has designed a very elegant way of direct repairing damaged DNA for many organisms. The virtually prevalent lesions formed past irradiation of Deoxyribonucleic acid by UV-B or UV-C are the result of photoreactions of pyrimidine bases. In particular, thymine dimers (T<>T) tin can form following photon absorption by a thymine monomer, intersystem crossing to its excited triplet country, and subsequent reaction with an adjacent thymine molecule.
Our group is involved in theoretical and computational studies of the photo-initiated, electron transfer catalyzed DNA repair mechanism carried out by the photolyase enzyme. The major effort in the past has been the written report of the electron transfer reaction. (come across Biophys. J., 76, 1241, 1999. and JACS 122. 1057, 2000.) The work on DNA repair began every bit a side project on the awarding of electron transfer theories that we have developed.
The nowadays thrust is toward an understanding of the molecular mechanism of photolyase and related issues of protein/Dna interactions. Our research is supported past the NSF funded Center for Biophotonics, CBST, here on campus.
The structure of the photolyase enzyme has been solved some time ago(1DNP), however the structure of the Dna/Photolyase complex remained unknown until the stop of 2004 (see below).
The topics we would like to address are:
i.) The mechanism of recognition of the dimers of Deoxyribonucleic acid by photolyase. Our previous work demonstrated that this is a very inticate question since the dimer is not 'flipped out' of the Deoxyribonucleic acid structure, but instead is 'poorly visible' on the surface of DNA unless photolyase is attached to it. ii.) The machinery of sliding/diffusion of photolyase along Dna. What has besides been suggested is that Dna itself may be processed through a fixed structure in the prison cell. 3.) In our previous piece of work we showed that upon binding of photolyase to a dimer on DNA, the latter is flipped out of the DNA helix, and gets positioned deep in the catalytic site of photolyase, close to the key redox co-factor FADH. In the repair reaction, this co-cistron, upon transfer of photoexcitation, is electronically excited, transfers an electron to the dimer, the latter splits, and an electron is then returned back to FADH. The mechanism past which photolyase flips the dimer needs to be clarified. 4.) Details of the repair reaction, which leads to the splitting of the dimer.
The figure below shows how the enzyme binds to Deoxyribonucleic acid.
December 2004 - Incredible news!!! The stucture of Dna/Photolyase complex is solved experimentally and reported in Scientific discipline. In our piece of work of 2000-2001 nosotros predicted the stucture of the complex, our prediction turned out to be correct to the modest details. Equally nosotros predicted, upon enzyme binding to the dimer, Deoxyribonucleic acid locally "melts", and the dimer flips out of the DNA helix.
How Does Dna Repair Enzyme Photolyase Prevent Skin Cancer,
Source: http://stuchebrukhov.ucdavis.edu/DNA_Repair/index.html
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