Navigation Links
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 rise to CPDs and (6-4) photoproducts are already well understood, this is not true for the Dewar lesion," says LMU chemist Professor Thomas Carell, who is also a member of the Center for Integrated Protein Science Munich (CiPSM), one of the Clusters of Excellence at LMU.

In a joint project within the SFB749 initiative Carells group together with research teams led by LMU physicist Professor Wolfgang Zinth (CiPSM) and Regina de Vivie-Riedle of the Department of Chemistry, could show that the backbone of the DNA plays a crucial role in the formation of the Dewar lesion. The backbone consists of repeating units made up of sugars and phosphates, which link the succession of bases that represent the protein-coding information in the DNA. "To our surprise, we found that the Dewar lesion can be generated only if the backbone in the affected region is intact," Carell explains. "If the continuity of the backbone is interrupted, or if the cross-linked base-pairs alone are exposed to sunlight, the Dewar structure fails to form." Thus, an interdisciplinary cooperation, which included chemists, physicists and theorists has, for the first time, been able to dissect the photochemical formation of the Dewar lesion at the atomic level. "Our results also show that the process is remarkably effective; indeed, this is one of the most efficient light-induced reactions known to occur within the DNA," says physicist Wolfgang Zinth.

Theoretical considerations yielded further insights into the details of the Dewar isomerization. "To follow the photochemical reaction dynamics on a high level of theory we came up with a hybrid method that separates the molecular system into subsystems treated on different quantum mechanical levels. This hierarchic strategy allows us to evaluate the dynamics of the complete system," says de Vivie-Riedle. Based on these calculations, the researchers were able precisely to define the role of the DNA backbone in the formation of the Dewar lesion. Cleavage of the backbone makes the molecule more flexible. Under these conditions, the (6-4) lesion will be protected and the system returns via a photophysical pathway back to its initial state. In contrast, an intact backbone keeps the molecule rigid, and strains the pyrimidine ring structure. The result is that only those atoms that must rearrange to form the Dewar isomer remain mobile, which favors the reaction that leads to the stable Dewar lesion.


'/>"/>

Contact: Luise Dirscherl
dirscherl@lmu.de
49-892-180-2706
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

Related biology news :

1. Conaway Lab identifies novel mechanism for regulation of gene expression
2. Rong Li Lab probes mechanism of asymmetry in meiotic cell division
3. Newly-discovered mechanism can explain the Beckwith-Wiedemann syndrome
4. Scientists unveil mechanism for up and down in plants
5. New cell division mechanism discovered
6. Corn researchers discover novel gene shut-off mechanisms
7. New regulatory mechanism discovered for cell identify and behavior in forming organs
8. Biomedical engineers detective work reveals antibiotic mechanism
9. Mechanisms of cardiovascular disease and cancer give clues to new therapies
10. Argonne scientists discover possible mechanism for creating handedness in biological molecules
11. A little wine boosts omega-3 in the body: Researchers find a novel mechanism for a healthier heart
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/20/2016)... 20, 2016  VoiceIt is excited to announce ... By working together, VoiceIt and VoicePass ... and VoicePass take slightly different approaches to voice ... security and usability. ... new partnership. "This marketing and technology ...
(Date:5/12/2016)... 12, 2016 WearablesResearch.com , a brand ... overview results from the Q1 wave of its quarterly ... was consumers, receptivity to a program where they would ... health insurance company. "We were surprised to ... Michael LaColla , CEO of Troubadour Research, "primarily ...
(Date:5/3/2016)...  Neurotechnology, a provider of high-precision biometric identification ... Identification System (ABIS) , a complete system for ... can process multiple complex biometric transactions with high ... face or iris biometrics. It leverages the core ... MegaMatcher Accelerator , which have been used in ...
Breaking Biology News(10 mins):
(Date:5/26/2016)... , ... May 26, 2016 , ... ... company, today announced several positive developments that position the Company for the future. ... of the transaction, Craig F. Kinghorn has been appointed Chairman of the Board, ...
(Date:5/25/2016)... ... May 25, 2016 , ... The Ankle Plating System 3 ... to address fractures of the distal tibia and fibula. This system marks Acumed's ... System 3 is composed of seven plate families that span the lateral, medial, ...
(Date:5/25/2016)... ... , ... WEDI, the nation’s leading authority on the use of health IT ... been named by the WEDI Board of Directors as WEDI’s president and CEO. Stellar ... more than 35 years of experience in healthcare, association management and organizational leadership, Stellar ...
(Date:5/24/2016)... 24, 2016   MedyMatch Technology Ltd ., the data ... real-time decision support tools in the emergency room, announced today ... Israeli Advanced Technology Industries (IATI) BioMed Conference. ... 15th National Life Sciences and Technology Week, and is ... Hotel in Tel Aviv, Israel . ...
Breaking Biology Technology: