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Watson-Crick Base Pairing is Responsible for DNA UV-Stability

Munich, September 5, 2014

An interdisciplinary research team of physicists and chemists at LMU could show, that the Watson-Crick base pairing is of fundamental importance for the UV-stability of natural DNA.

The fascinating double helical structure of the DNA has been discovered by Watson and Crick over 60 years ago. It is stabilized by two main interactions – the base stacking between neighbouring bases and the base pairing by hydrogen bonds between bases on opposite strands. The base pairing scheme between Guanine and Cytosine as well as Adenine and Thymine is essential for replication and preservation of genetic information.

The groups of Prof. Zinth (Chair of BioMolecular Optics) and Prof. Carell (Chair of Bioorganic Chemistry), particularly Dominik Bucher and Alexander Schlüter, used a combination of femtosecond infrared spectroscopy and bioorganic chemistry to elucidate a new function of the base pairing: it protects DNA from photodamage.

UV-radiation is known to induce photochemical reactions in the DNA, causing changes in its structure. These alterations in the genetic code can lead to cell death or cancer. In a very recent study, the authors could show that UV-radiation may generate charged radicals in synthetic DNA single strands. These reactive radicals are known to damage DNA. In their new study, the authors investigated natural double stranded calf thymus DNA. After excitation with short laser pulses, the researchers discovered an unexpected simple deactivation mechanism of the dangerous excited states: Each excited base pair – Guanine and Cytosine as well as Adenine and Thymine – decays in a concerted way back to the ground state. Thus, the Watson-Crick base pairing controls the dissipation of the absorbed UV energy. This contradicts the scientific consensus, that the base sequence within one strand is responsible for the deactivation of excited states. A second important finding of the study concerns the biological consequences. The Watson-Crick base pairing annihilates the dangerous states generated by UV-light in DNA strands. Thus, Watson-Crick base pairing acts as a natural "sunscreen" and is of fundamental importance to enable life under UV-radiation.

The work was supported by the Deutsche Forschungsgemeinschaft (SFB 749, TP A4 and A5, Clusters of Excellence “Center for Integrated Protein Science Munich (CIPSM)” and “Munich-Center for Advanced Photonics” (MAP)).

Publication:

“Watson-Crick Base Pairing Controls the Excited-State Decay in Natural DNA” Dominik B. Bucher, Alexander Schlueter, Thomas Carell and Wolfgang Zinth, Angew. Chem. Int. Ed, 2014, early edition, DOI: 10.1002/anie.201406286

Selected as a “Very Important Paper”

Link: http://onlinelibrary.wiley.com/doi/10.1002/anie.201406286/abstract