Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study reveals how enzyme detects ultraviolet light damage

23.08.2018

Damage to DNA is a constant threat to cellular life, and so it is constantly monitored and detected by a family of enzymes called RNA polymerases, resulting in subsequent repair to maintain genome integrity. In a paper published this week in the journal PNAS, researchers at University of California San Diego School of Medicine, with colleagues in Spain and Finland, describe for the first time how one type of RNA polymerase gets stalled by DNA lesions caused by exposure to ultraviolet (UV) light.

Called thymine dimers, DNA lesions are damage sites to the base pairs that comprise the structure of DNA. The DNA lesions are caused by exposure to UV light, such as sunlight, which causes neighboring thymine base pairs to bond, disrupting the DNA strand. Untreated, these lesions may eventually result in cancerous growths, such as melanoma.


Ultraviolet radiation, such as sunlight, can damage cellular DNA, leading to cancer. UC San Diego researchers have described the underlying mechanism that helps explain why such damage isn't always repaired.

Image collage courtesy of Dong Wang, UC San Diego

RNA polymerase I (Pol I) is an enzyme responsible for up to 60 percent of total transcriptional activity in growing cells. It is a key determinant for cell growth control, and is also responsible for identifying lesions and activating repairs at the rDNA region, a DNA sequence that codes for ribosomal RNA.

"It's the most active RNA polymerase in growing cells and so its ability to identify lesions has significant influence on whether a cell can survive UV-caused genetic damage," said co-corresponding author Dong Wang, PhD, associate professor in the Skaggs School of Pharmacy and Pharmaceutical Sciences and the Department of Cellular and Molecular Medicine at UC San Diego. "However, little is known about how this enzyme actually processes UV-induced lesions."

In the new study, Wang's lab, in collaboration with Carlos Fenandez-Tornero, PhD, molecular biologist, and colleagues at the Spanish National Research Council in Madrid, combined in vitro enzymatic activity studies with electron cryomicroscopy to characterize the mechanisms that stall Pol I as it approaches a lesion to begin recruiting proteins responsible for DNA repair.

They found that Pol I is able to sense the DNA lesion through specific interactions with both the damaged base and the DNA backbone, stalling right before the lesion reaches the active site of RNA Pol I.

Additionally, the study identified a key amino acid among more than 5,000 that constitute Pol I that is essential to detecting DNA lesions formed by UV damage. Interestingly, this Pol I-specific residue does not exist in other forms RNA polymerases. Mutation studies suggest that this residue is important in controlling the polymerase stall profile at DNA lesions.

Because RNA Pol I is a key determinant for cell growth control, it is also an attractive cancer therapeutic target, said Wang, who suggested the findings could open a new avenue for the development of novel anticancer drugs that target RNA Pol I transcription machinery.

###

Co-authors include: Marta Sanz-Murillo and Maria Moreno-Morcillo, Spanish National Research Council; Jun Xu, UC San Diego; Georgiy A. Belogurov, University of Turku, Finland; Olga Calvo, Spanish National Research Council and University of Salamanca, Spain; and David Gil-Carton, Cooperative Center for Research in Biosciences, Spain.

Media Contact

Scott LaFee
slafee@ucsd.edu
858-249-0456

 @UCSanDiego

http://www.ucsd.edu 

Scott LaFee | EurekAlert!

Further reports about: DNA RNA RNA polymerase cell growth enzyme lesions ultraviolet ultraviolet light

More articles from Health and Medicine:

nachricht Novel anti-cancer nanomedicine for efficient chemotherapy
17.09.2019 | University of Helsinki

nachricht Researchers have identified areas of the retina that change in mild Alzheimer's disease
16.09.2019 | Universidad Complutense de Madrid

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Happy hour for time-resolved crystallography

Researchers from the Department of Atomically Resolved Dynamics of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg, the University of Hamburg and the European Molecular Biology Laboratory (EMBL) outstation in the city have developed a new method to watch biomolecules at work. This method dramatically simplifies starting enzymatic reactions by mixing a cocktail of small amounts of liquids with protein crystals. Determination of the protein structures at different times after mixing can be assembled into a time-lapse sequence that shows the molecular foundations of biology.

The functions of biomolecules are determined by their motions and structural changes. Yet it is a formidable challenge to understand these dynamic motions.

Im Focus: Modular OLED light strips

At the International Symposium on Automotive Lighting 2019 (ISAL) in Darmstadt from September 23 to 25, 2019, the Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, a provider of research and development services in the field of organic electronics, will present OLED light strips of any length with additional functionalities for the first time at booth no. 37.

Almost everyone is familiar with light strips for interior design. LED strips are available by the metre in DIY stores around the corner and are just as often...

Im Focus: Tomorrow´s coolants of choice

Scientists assess the potential of magnetic-cooling materials

Later during this century, around 2060, a paradigm shift in global energy consumption is expected: we will spend more energy for cooling than for heating....

Im Focus: The working of a molecular string phone

Researchers from the Department of Atomically Resolved Dynamics of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg, the University of Potsdam (both in Germany) and the University of Toronto (Canada) have pieced together a detailed time-lapse movie revealing all the major steps during the catalytic cycle of an enzyme. Surprisingly, the communication between the protein units is accomplished via a water-network akin to a string telephone. This communication is aligned with a ‘breathing’ motion, that is the expansion and contraction of the protein.

This time-lapse sequence of structures reveals dynamic motions as a fundamental element in the molecular foundations of biology.

Im Focus: Milestones on the Way to the Nuclear Clock

Two research teams have succeeded simultaneously in measuring the long-sought Thorium nuclear transition, which enables extremely precise nuclear clocks. TU Wien (Vienna) is part of both teams.

If you want to build the most accurate clock in the world, you need something that "ticks" very fast and extremely precise. In an atomic clock, electrons are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Society 5.0: putting humans at the heart of digitalisation

10.09.2019 | Event News

Interspeech 2019 conference: Alexa and Siri in Graz

04.09.2019 | Event News

AI for Laser Technology Conference: optimizing the use of lasers with artificial intelligence

29.08.2019 | Event News

 
Latest News

Stroke patients relearning how to walk with peculiar shoe

18.09.2019 | Innovative Products

Statistical inference to mimic the operating manner of highly-experienced crystallographer

18.09.2019 | Physics and Astronomy

Scientists' design discovery doubles conductivity of indium oxide transparent coatings

18.09.2019 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>