Bistranded Oxidized Purine Damage Clusters:  Induced in DNA by Long-Wavelength Ultraviolet (290−400 nm) Radiation?

Abstract

Bistranded clustered DNA damages involving oxidized bases, abasic sites, and strand breaks are produced by ionizing radiation and radiomimetic drugs, but it was not known whether they can be formed by other agents, e.g., nonionizing radiation. UV radiation produces clusters of cyclobutyl pyrimidine dimers, photoproducts that occur individually in high yield. Since long-wavelength UV (290-400 nm) radiation induces oxidized bases, abasic sites, and strand breaks at low yields, we tested whether it also produces clusters containing these lesions. We exposed supercoiled pUC18 DNA to UV radiation with wavelengths of >290 nm (UVB plus UVA radiation), and assessed the induction of bistranded clustered oxidized purine and abasic clusters, as recognized by Escherichia coli Fpg protein and E. coli Nfo protein (endonuclease IV), respectively, as well as double-strand breaks. These three classes of bistranded clusters were detected, albeit at very low yields (37 Fpg-OxyPurine clusters Gbp(-1) kJ(-1) m(2), 8.1 double-strand breaks Gbp(-1) kJ(-1) m(2), and 3.4 Nfo-abasic clusters Gbp(-1) kJ(-1) m(2)). Thus, these bistranded OxyPurine clusters, abasic clusters, and double-strand breaks are not uniquely induced by ionizing radiation and radiomimetic drugs, but their level of production by UVB and UVA radiation is negligible compared to the levels of frequent photoproducts such as pyrimidine dimers.

After double-strand break induction by UV-A, homologous recombination and nonhomologous end joining cooperate at the same DSB if both systems are available

“…It is assumed that these DSBs are generated by clustered SSBs that occur in close proximity in the nucleus (Jenner et al, 2001), at sites where the endogenous photosensitisers are localised. In contrast to cell-free systems, where no DSBs are found after UV-A exposure (Song et al, 2002), the DSB induction is strictly dependent on the cellular environment (De Gruijl et al, 2001;Griffiths et al, 1998).…”

Clustered abasic lesions profoundly change the structure and stability of human telomeric G-quadruplexes

“…UV radiation is generally believed to produce only clusters of cyclobutane pyrimidine dimers but long-wavelength UV (290–400 nm) radiation also creates oxidized bases, AP sites, and strand breaks, albeit in low yield. The number of these clusters due to UVB and UVA is negligible compared to the levels of pyrimidine dimers but they cannot be ignored (17). …”

AtREV1, a Y-Family DNA Polymerase in Arabidopsis, Has Deoxynucleotidyl Transferase Activity in Vitro

“…The 6-4 photoproducts (6-4PP) and Dewar isomer, a derivative of 6-4PP, correspond to most of the remainder (20%-24%; Mitchell, 1995;Cadet et al, 2005). Other types of DNA damage, including 8-oxoG, pyrimidine hydrate, thymine glycol, DNA single-strand break, etc., are generated by UV-B radiation at very low yield (,0.1%-2%;Mitchell, 1995;Gao and Murphy, 2001;Song et al, 2002;Cadet et al, 2005;Friedberg et al, 2006). On the other hand, apurine/apyrimidine (AP) sites are among the most abundant DNA lesions generated spontaneously (Boiteux and Guillet, 2004).…”

“…The AP site also is generated when exposed to the various DNA-damaging agents, such as ionizing radiation and alkylating chemicals, through the reaction of DNA N-glycosylases that remove the damaged base . The AP sites are rarely formed after UV irradiation directly (Song et al, 2002) or as a consequence of a cellular process removing the damaged base . Such lesions can lead to incorporation of the wrong base or can inhibit DNA replication and transcription, resulting in mutations and cell death (Britt, 1999).…”