Rita and John Cornforth Award 2016 Winner
Dublin-Reading DNA Consortium
University of Reading, University of Dublin, Trinity College, University College Dublin
Awarded for their structural work on DNA - transition metal complexes, proof of the origins of the "light-switch" effect and its implications for mechanisms of DNA damage
About the Winner
Understanding the factors that determine the effectiveness of metal complexes as DNA photo-probes and as sensitisers for the light-induced damage to nucleic acids requires a multidisciplinary approach. One key problem in the area, which can often not be determined accurately from solution studies, is to know exactly where and how the probe molecule is bound to the DNA strand. For example this has been an area of controversy with intercalating ruthenium polypyridyl complexes, which are known as versatile probes and photosensitisers (and on which Professor Kelly has worked since the 1980s).
Potentially crystallography offers a precise solution to this problem, but it requires a laboratory who have specialised knowledge of nucleic acid crystallography. Indeed no crystal structure of the ruthenium complexes bound to DNA had been reported until this was successfully achieved in the laboratory of Professor Cardin in the first stage of the collaboration with Dublin.
The team has gone on to solve the structure of more than 15 related systems. Another major challenge in the area of DNA-photoprobes is to understand the mechanism of the photo-processes involved, which means being able to identify and determine the very rapidly reacting intermediates involved. Since 2005 Dr. Quinn and Professor Kelly have been users of the outstanding facilities of the Ultrafast Laser Laboratory in Rutherford-Appleton so as to monitor such intermediates in solution.
In 2013 Cardin, Kelly and Quinn were awarded access to the Laser Laboratory to attempt to study the ultrafast processes in DNA crystals, which would allow reactions such as photo-oxidation to be studied with a degree of precision not previously possible. The first results of this work have recently been published and reports the electron transfer reaction between the ruthenium polypyridyl photosensitiser and a specific guanine in a mixed sequence DNA.