GENETIC AND MOLECULAR ANALYSIS OF DNA DAMAGE REPAIR AND TOLERANCE PATHWAYS - Environmental UV Radiation: Impact on Ecosystems and Human Health and Predictive Models - page 107

upon which the dimer is monomerized and the enzyme is released to seek another
dimer. It is important to note that the formation of the enzyme-substrate complex is
temperature-dependent, and also dependent on the concentration of the enzyme (number
of photolyases per cell) and concentration of the substrate (CPD in DNA). The
photolytic reaction depends on the wavelength and concentration (intensity) of the
second substrate, the photon, but is virtually independent of temperature. Further, the
enzyme-substrate complex is remarkably stable in the dark, allowing dissection of the
two component reactions, i.e., enzyme-substrate complex formation and dimer
photolysis.
4. Nucleotide Excision Repair
Nucleotide excision repair deals with a wide variety of bulky lesions in DNA, including
CPD. Several enzymes are required (including a nuclease, polymerase, ligase and other
Figure 4. Repair of CPD in DNA by nucleotide excision repair.
proteins), and nucleoside triphosphates are used as an energy source. In addition to UV
damages, this path deals with DNA alterations induced by some chemicals and even by
ionizing radiation.
5. Base Excision Repair
Base excision repair deals with altered bases in DNA through a glycosylase activity,
which removes the altered base leaving an abasic site, followed by a lyase-mediated
cleavage of the phosphodiester backbone, and removal of the abasic site and restoration
of the DNA by some of the proteins involved in nucleotide excision repair. The
glycosylase and lyase activities may reside in the same protein or may involve separate
enzymes. Abasic sites (sites of base loss) are dealt with by endonucleases that
recognize and cleave the DNA at abasic sites. In human cells, an important enzyme in