Remote Photodamaging of DNA by Photoinduced Energy Transport

Abstract

Local DNA photodamaging by light is well-studied and leads to a number of structurally identified direct damage, in particular cyclobutane pyrimidine dimers, and indirect oxidatively generated damage, such as 8-oxo-7,8-hydroxyguanine. Similar damages have now been found at remote sites, at least more than 105 Å (30 base pairs) away from the site of photoexcitation. In contrast to the established mechanisms of local DNA photodamaging, the processes of remote photodamage are only partially understood. Known pathways include those to remote oxidatively generated DNA photodamages, which were elucidated by studying electron hole transport through the DNA about 20 years ago. Recent studies with DNA photosensitizers and mechanistic proposals on photoinduced DNA-mediated energy transport are summarized in this minireview. These new mechanisms to a new type of remote DNA photodamaging provide an important extension to our general understanding to light-induced DNA damage and their mutations.

Direct Observation of Excitation Wavelength-Dependent Ultrafast Intersystem Crossing in Cytosine Nucleoside Solution

“…Furthermore, it is our hope that our results could benchmark the future calculations that aim to reveal the key vibrational mode that accounts for the ultrafast ISC in dCyd. The elucidation of the ISC mechanism in dCyd is important because a long-lived triplet excited state could lead to the formation of deleterious photoproducts in both DNA and RNA. − Therefore, this study also paves the path to further study dCyd triplet state-involved photophysical and photochemical properties in DNA and RNA.…”

“…Ultraviolet (UV) radiation-initialized photochemical reactions are one of the greatest threats to the biological genome on Earth since all canonical nucleobases, which are building blocks of DNA/RNA, absorb strongly in the UVC region (<280 nm). Fortunately, these DNA bases can dissipate over 90% of their excited-state energy through efficient non-radiative channels to the ground state, which guarantees the intrinsic photostability of nucleic acid. − However, increasing evidence has shown that photophysics and photochemistry in DNA and RNA are also associated with longer-lived excited states such as lower-lying dark nπ* states − and triplet excited states. − In particular, triplet excited states are of special interest as they can lead to photolesions such as cyclobutene pyrimidine dimers (CPDs), pyrimidine (6–4) pyrimidone photoproducts, one-electron oxidation, H-abstraction, and intrabase cross-link in DNA and RNA. − Therefore, it is essential to understand triplet state-involved excited-state dynamics in DNA/RNA as it can provide the chemical reaction mechanism for the above-mentioned photolesions.…”

Chemiexcited Neurotransmitters and Hormones Create DNA Photoproducts in the Dark

“…Relative chemiluminescence was calculated with respect to the control experiment containing ONOO − with no substrate, defined as 1.0 (raw data in Figures S1−S5 singlet oxygen. 22 Therefore, they are not expected to emit chemiluminescence. The signal for all compounds (except the flavins) was 2-to 7-fold above background, with melatonin oxidation producing the highest luminescence emission intensity (Figures 2a and S1−S4).…”

Topology and Excited State Multiplicity as Controlling Factors in the Carbazole-Photosensitized CPD Formation and Repair

“…Moreover, how far the energy migrates in DNA to eventually produce photodamage is still a matter of concern. 35 , 36 …”

“…As a matter of fact, Cbz can be excited selectively in the presence of Thy, and also, Cbz exhibits a moderate intersystem crossing quantum yield (0.36), a relatively high triplet energy (70.2 kcal mol –1 ), a ππ* triplet configuration (free from the problems associated with the competitive hydrogen abstraction by benzophenone), and a reasonably long-living triplet excited state. Moreover, how far the energy migrates in DNA to eventually produce photodamage is still a matter of concern. , …”