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 Lethal combination: Drug cocktail turns off the juice to cancer cells
12.12.2018 | Universität Basel

nachricht Smelling the forest – not the trees
12.12.2018 | Universität Konstanz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Success at leading conference on silicon materials science and technology in Japan

13.12.2018 | Awards Funding

NSF-supported scientists present new research results on Earth's critical zone

13.12.2018 | Earth Sciences

Barely scratching the surface: A new way to make robust membranes

13.12.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>