Photobiological Origins of the Field of Genomic Maintenance

Abstract

Although sunlight is essential for life on earth, the ultraviolet (UV) wavelengths in its spectrum constitute a major threat to life. Various cellular responses have evolved to deal with the damage inflicted in DNA by UV, and the study of these responses in model systems has spawned the burgeoning field of DNA repair. Although we now know of many types of deleterious alterations in DNA, the approaches for studying them and the early mechanistic insights have come in large part from pioneering research on the processing of UV-induced bipyrimidine photoproducts in bacteria. It is also notable that UV was one of the first DNA damaging agents for which exposure was directly linked to cancer; the sun-sensitive syndrome, xeroderma pigmentosum, was the first example of a cancer-prone hereditary disease involving a defect in DNA repair. We provide a short history of advances in the broad field of genomic maintenance as they have emerged from research in photochemistry and photobiology.

Figure 1

Wavelength distribution of sunlight impacting earth’s atmosphere and the selective attenuation of short UV wavelengths by ozone, molecular oxygen and water vapor. (Ranges: UVA, 315–400 nm; UVB 280–315 nm; UVC 100–280 nm). Adapted by Graciela Spivak from http://ozonewatch.gsfc.nasa.gov/facts/SH.html.

Figure 2

Schematic representation of NER in Escherichia coli. Damage can be recognized either by sensing instability of the duplex DNA structure (for GGR) or by the arrest of a translocating RNA polymerase upon encountering the damaged site (for TCR). In the latter case Mfd binds the arrested polymerase and recruits UvrA, which then further recruits UvrB, as the polymerase and RNA product are released. From then on the pathway proceeds in the classic manner in which the recognition proteins recruit UvrC, which catalyzes dual incisions (~ 13 nt) in the damaged strand. UvrD and DNA Pol I excise the damaged stretch and Pol I synthesizes a repair patch that is eventually ligated to the contiguous parental strand. The relative sizes of the nucleic acids and proteins depicted in this figure are not meant to reflect their actual sizes and conformations.