UV-Induced Charge Transfer States in DNA Promote Sequence Selective Self-Repair

Abstract

Absorption of UV-radiation in nucleotides initiates a number of photophysical and photochemical processes, which may finally cause DNA damage. One major decay channel of photoexcited DNA leads to reactive charge transfer states. This study shows that these states trigger self-repair of DNA photolesions. The experiments were performed by UV spectroscopy and HPLC on different single and double stranded oligonucleotides containing a cyclobutane pyrimidine dimer (CPD) lesion. In a first experiment we show that photoexcitation of adenine adjacent to a CPD has no influence on this lesion. However, excitation of a guanine (G) adenine (A) sequence leads to reformation of the intact thymine (T) bases. The involvement of two bases for the repair points to a long-living charge transfer state between G and A to be responsible for the repair. The negatively charged A radical anion donates an electron to the CPD, inducing ring splitting and repair. In contrast, a TA sequence, having an inverted charge distribution (T radical anion, A radical cation), is not able to repair the CPD lesion. The investigations show that the presence of an adjacent radical ion is not sufficient for repair. More likely it is the driving power represented by the oxidation potential of the radical ion, which controls the repair. Thus, repair capacities are strongly sequence-dependent, creating DNA regions with different tendencies of self-repair. This self-healing activity represents the simplest sequence-dependent DNA repair system.

Photochemical Formation of Cyclobutane Pyrimidine Dimers in DNA through Electron Transfer from a Flanking Base

“…Cyclobutane pyrimidine dimer (CPD) is a photoproduct known to interfere with many important cellular processes, thereby potentially leading to skin cancer . The prevention of CPD formation works through an electron transfer (ET) from an external moiety, such as a flanking guanine, or an excimer which have been reported as electron donors. ET is also involved in CPD repair by DNA photolyase where a crucial step is ET from its cofactor to CPD.…”

Chemical excitation of electrons: A dark path to melanoma

“…Preventing both strands from being damaged at the same site allows the undamaged complementary strand to be used as a template for DNA excision repair [52]. Third, photoexcited bases repair nearby CPDs [53]. Excitation of an excimer of G and A on the same strand leads to a charge separation, with the excess electron going to A.…”

Two-dimensional electronic spectroscopy as a tool for tracking molecular conformations in DNA/RNA aggregates

“…Nuclebase stacking might indeed increase their excited state lifetime and potentially make them more prone to photochemical mutations, [4][5][6][7] in contrast to the efficient and ultrafast decay registered in isolated nucleobases, 8,9 which is expected to strongly promote its photo-protection mechanisms. 10 This effect, believed to strongly modulate the complexity of DNA photophysics, 11,12 is particularly hard to measure within standard pump-probe set-ups, the experimental workhorse in photochemistry. In standard 1D pump-probe spectroscopy, different signals from diverse molecular motifs overlap strongly in space and time, leading to highly congested spectral regions whose complex interpretation remains elusive.…”