Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Enzyme, lost in most mammals, is shown to protect against UV-induced skin cancer

26.01.2005


In a finding that broadens our insight into the cause of certain kinds of UV-induced skin cancer, researchers at Erasmus University Medical Center (Rotterdam, The Netherlands) have employed an evolutionarily ancient enzyme-repair system to identify the principal type of DNA damage responsible for the onset of skin-tumor development. The researchers’ findings also suggest that this enzyme system may be useful in developing preventative therapies against skin cancer.



Ultraviolet light is a known source of damage to our DNA, but under normal conditions humans and other mammals are capable of removing UV-induced DNA damage by a DNA repair mechanism called nucleotide excision repair. Insufficient repair of UV-induced DNA damage, which for example may occur after excessive unprotected sunbathing, can lead to cellular death – recognized as sunburn of the skin – and may cause permanent changes in the DNA (mutations) that ultimately can result in the onset of skin cancer. Thus far it was not clear how the two major types of UV-induced DNA lesions – cyclobutane pyrimidine dimers (CPDs) and (6-4)photoproducts (6-4PPs) – contribute to the processes of cell death and cancer formation. Identifying the relative contributions of the two types of damage to tumor formation is critical for the development of therapies that could help prevent skin cancer. Moreover, CPDs and 6-4PPs have particular potential to cause lasting damage to mammalian cells because photolyases – a class of enzymes capable of efficiently repairing these lesions – have apparently been lost from placental mammals over the course of evolution.

Thus, most mammals, including humans, can only repair these lesions through a much less direct and elaborate process called nucleotide excision repair.


In the new work, Dr. Bert van der Horst and colleagues studied the effects of CPD and 6-4PP lesions by providing mice with transgenes encoding CPD and 6-4PP photolyase enzymes.

Although mice do not ordinarily produce these enzymes, which remove either CPD or 6-4PP lesions by using visible light as an energy source, expression of the transgenes allowed rapid photolyase-mediated repair of these lesions. The researchers found that transgenic mice bearing the CPD photolyase transgene, in contrast to mice bearing the 6-4PP photolyase transgene, showed superior resistance to the deleterious effects of UV irradiation. Not only could CPD photolyase transgenic animals withstand doses of UV light that cause severe sunburn in normal mice, but they also showed superior resistance to UV-induced skin cancer. This work clearly points to CPD lesions as the major intermediate in UV-induced cellular damage leading to non-melanoma skin cancer. Importantly, it also suggests that photolyases may be successfully employed as a genetic tool to combat UV-induced skin cancer.

Judith Jans, Wouter Schul, Yurda-Gul Sert, Yvonne Rijksen, Heggert Rebel, Andre P.M. Eker, Satoshi Nakajima, Harry van Steeg, Frank R. de Gruijl, Akira Yasui, Jan H.J. Hoeijmakers, Gijsbertus T.J. van der Horst: "Powerful Skin Cancer Protection by a CPD-Photolyase Transgene"

The other members of the research team include Judith Jans of Erasmus University Medical Center, Rotterdam, presently at University of California, Berkeley; Wouter Schul of Erasmus University Medical Center, Rotterdam and Tohoku University; Yurda-Gul Sert, Yvonne Rijksen, Andre P.M. Eker, Jan H.J. Hoeijmakers, and Gijsbertus T.J. van der Horst of Erasmus University Medical Center, Rotterdam; Heggert Rebel and Frank R. de Gruijl of Leiden University Medical Center; Satoshi Nakajima of Novartis, Institute of Tropical Disease, Singapore; Harry van Steeg of National Institute of Public Health and the Environment in Bilthoven, The Netherlands; and Akira Yasui of Tohoku University. This work was supported by the Dutch Cancer Foundation, the Association for International Cancer Research, and the Japanese Ministry of Education, Science, and Culture.

Heidi Hardman | EurekAlert!
Further information:
http://www.current-biology.com
http://www.cell.com

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>