Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study finds direction of enzymes affects DNA repair

23.06.2003


DNA repair enzymes do a much better job of repairing damaged genes if they are facing in one direction instead of the other. This and other details of how DNA repair is performed are reported in the online version of the journal Proceedings of the National Academy of Sciences by researchers at Washington State University and the National Institute of Environmental Health Sciences.

According to the new study, the repair enzymes "distinguish" between various positions and may be two to three times as effective, depending on whether the damage to be repaired is facing "toward" or "away from" the nucleosome, the protein-DNA complex that folds the very long DNA strands into the tiny nucleus of a cell and gives enzymes access to the DNA for repair and for replication when the cell divides.

Washington State’s senior author, Michael J. Smerdon, explained, "Like a child’s face, our DNA gets smudged up all the time by environmental and bodily chemicals. Our work provides additional details about how our cells work to clean the DNA up - to correct our heredity molecule, the DNA helix that is within each living cell." The explosion of research on DNA repair dates back less than a decade, to the demonstration that some colon cancer and xeroderma pigmentosum are linked to faulty DNA repair. Xeroderma pigmentosum is a rare condition in which the skin is extremely sensitive to the sun and other ultraviolet light, resulting in extreme freckling and aging.



A key element of the report is the finding of a strong "down-regulation" of one of the repair enzymes, DNA polymerase ß (pol ß) in the presence of the nucleosome. This means that nucleosome formation on DNA can inhibit base excision repair of a nucleosome-sequestered DNA lesion. Such down-regulation could have huge biological implications, since repair of such DNA damage will be blocked at the pol ß step. Such a blocking of repair will ultimately lead to mutations or other genomic instability or will interrupt cell growth.

"This changes our thinking about nucleosomes and base excision repair," Samuel Wilson, M.D., Ph.D., deputy director of NIEHS and its researcher on the project, said. "We are still just scratching the surface of the study of cellular regulation, but the potential seems clear. The findings demonstrate how close we are to the day when, if the body fails to make the right regulatory corrections, physicians may be able to step in and make them anyway. In other words, to make corrections before diseases - a cancer or Alzheimer’s, for example - can develop."

Brian C. Beard, Ph.D., of WSU’s School of Molecular Biosciences carried out the study under the guidance of Drs. Smerdon and Wilson.

The double-coil shape of the DNA molecule which manages our heredity and directs our cells was described 50 years ago. Almost immediately, it became clear that toxic agents in the environment and in the body can produce adverse changes in the DNA. Handily, however, these alterations are generally repaired by the body’s mechanisms, much the way "spell check" repairs misspelled words on a computer. Actually, it is much more complicated than that:

In repairing some 10,000 to 20,000 DNA adducts or lesions that occur each day in each of a human’s 10 trillion cells, repair enzymes travel up and down the double helix strands of DNA until they find a damaged area. The enzymes cut out the lesion and fill the gap with fresh DNA.

All this is performed in very tight quarters. Each human cell has a strand of DNA that is almost two meters long. This is tightly coiled in the bead-like nuclerosomes and densely folded in order to fit inside the tiny nucleus of the cell.

Repairs are complicated by this compact packaging, and Dr. Smerdon has shown that repair of damage cannot proceed until the DNA is unfolded.

He said recently that understanding the repair of DNA in specific regions of the packaged structure in the cell nucleus is "crucial to understanding why certain DNA lesions are not repaired for long times in human cells. Such ’long-lived’ lesions can form mutations and ultimately lead to cancer."

In 1978, Dr. Smerdon received a Young Environmental Scientist Award from NIEHS, which has continued to support his research. In 2002, NIEHS awarded Dr. Smerdon a ten-year $3.58 million MERIT - Method to Extend Research in Time - award to further his groundbreaking studies.


###
Dr. Smerdon can be reached at smerdon@mail.wsu.edu or (509) 335-6853
Dr. Wilson can be reached at wilson5@nieh.nih.gov or (919) 541-3267
Dr. Beard can be reached at brianc@mail.wsu.edu

Additional Contact:
Tom Hawkins, (919) 541-1402

Bill Grigg | EurekAlert!
Further information:
http://www.niehs.nih.gov/

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>