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When inflexibility is counterproductive: Mechanism of UV-induced DNA Dewar lesion revealed
Date:11/28/2011

Excessive exposure to ultraviolet (UV) radiation of sunlight can result in skin damage and may even induce skin cancers. Irradiation with UV light causes mutations in the DNA, which can interfere with or even inhibit the read-out of genetic information and hence affect the cell function. The Dewar lesion is one of the major UV-induced reaction products, which can itself generate mutations. Understanding the mechanism that leads to the formation of the Dewar lesion is therefore of great interest.Researchers from Ludwig-Maximilians-Universitaet (LMU) in Munich have now shown that the DNA backbone (the double-stranded scaffold which bears the subunits that encode the genetic information) plays a decisive role in the process. The Dewar lesion can be generated only if the backbone of the DNA is intact. If the DNA strand itself is broken, and therefore more flexible, the Dewar reaction will not take place. The process reveals a surprisingly paradoxical facet of the DNA structure. On the one hand, an unbroken backbone is a prerequisite for DNA function and for cell survival; on the other, the intact backbone favors the formation of Dewar lesions upon exposure to UV, and so facilitates UV-induced mutagenesis. (Angewandte Chemie, 23 November 2011)

UV radiation induces molecular changes in DNA structure, which can lead to genetic mutations and finally to cell death. Energetic UV light primarily produces two types of photochemical damage in the subunits of the DNA - cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts. Both types of lesion are due to cross-linking of adjacent pyrimidine bases on the same DNA strand. Continued exposure to UV light transforms the (6-4) photoproduct into a Dewar lesion by inducing further structural changes. Dewar lesions are stable end-products of continuous exposure to sunlight. Moreover, they are highly mutagenic, i.e. they can themselves induce a range of further mutations. "While the chemical changes that give
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Contact: Luise Dirscherl
dirscherl@lmu.de
49-892-180-2706
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

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