Title :

Investigations into Mechanism of Sequence and Conformation Specific Photo-induced DNA Self-repair

Abstract :

The study of UV-induced photo-damage and repair of nucleic acids is fascinating due to its connections to the molecular origins of life. The role of sunlight is particularly interesting as it not only served as a source of energy for forming new molecules but also quite likely broke down what formed, creating a cycle in which only the toughest could survive. Many molecules of life, including the canonical nucleobases, are thought to have emerged from this competition between photo-creation and photo-destruction. Naturally, their photo-stability would make them ideal building blocks for more complex structures. Despite this the nucleobases are not completely immune to chemical and radiation induced damage. In fact, DNA absorbs in the UV region of solar spectrum and undergoes several photophysical and photochemical processes which lead to formation of harmful photoproducts like cyclobutane pyrimidine dimers (CPDs), 6-4 photo lesion etc. Enzymatic machineries have evolved which can selectively repair different types of photodamage.1 However, in the absence of such sophisticated machinery when life initially evolved, it is tempting to speculate that the nucleotide sequences could be capable of self-repair.2 Investigations into such a self-repair mechanism has received a lot of attention due to the interesting photophysics involved and connections to chemical evolution.3-5 Recently, a tetranucleotide sequence (GATT) was reported to have inherent capability to repair a CPD lesion via a sequence specific sequential electron transfer.6 The details of the mechanisms and the sequence specificity has yet to be rationalized. I will present our findings revealing the possibility of photoinduced self-repair in a commonly occurring tetranucleotide sequence, TTAG. By employing a judicious combination of linear response and real time time-dependent density function theory, we obtain a detailed description of the mechanism of repair, the states involved at the various stages, factors influencing the forward and backward electron transfer as well as the driving force for the CPD repair. We find that, in contrast to the GATT sequence, the forward electron transfer process is promoted by a crucial ultrafast excitation energy transfer (EET) across the nucleobases resulting in charge-injection into the CPD dimer. The conditions favouring this EET are absent in the spectra of other conformations of the same sequence, indicating conformation specificity to the mechanism in addition the sequence specificity. Using examples from our research I will also emphasise on the challenges faced by current theoretical approaches to answer questions posed in the field.


1. https://www.nobelprize.org/uploads/2018/06/popular-chemistryprize2015.pdf

2. Beckstead, A. A.; Zhang, Y.; de Vries, M. S.; Kohler, B., Phys. Chem. Chem. Phys., 2016,18, 24228-24238

3. M. R. Holman , T. Ito and S. E. Rokita , J. Am. Chem. Soc., 2007, 129 , 6-7.

4. D. J. F. Chinnapen and D. Sen , Proc. Natl. Acad. Sci. U. S. A., 2004, 101 , 65-69.

5. N. Khiem Van and C. J. Burrows , Acc. Chem. Res., 2012, 45 , 2151-2159.

6. Bucher, D. B.; Kufner, C. L.; Schlueter, A.; Carell, T.; Zinth, W., J. Am. Chem. Soc. 2015, 138, 186–190. ; Szabla, R.; Kruse, H.; Stadlbauer, P.; Sponer, J.; Sobolewski, A. L. Chem. Sci. 2018, 9, 3131–3140.