Featured Research

from universities, journals, and other organizations

Molecular engines star in new model of DNA repair

Date:
January 8, 2014
Source:
NYU Langone Medical Center / New York University School of Medicine
Summary:
In a new study, researchers reveal how an enzyme called RNA polymerase patrols the genome for DNA damage and helps recruit partners to repair it. The result: fewer mutations and consequently less cancer and other kinds of disease.

A new model of DNA repair is revealed in a new study. In this model, RNA polymerase patrols tracks of double-stranded DNA and stalls over damaged areas. An enzyme called UvrD helicase pulls the blocked RNA polymerase off the tracks, exposing broken DNA to repair. After the repair, the polymerase continues along the tracks.
Credit: NYU Langone Medical Center

Our health depends in large part upon the ability of specialized enzymes to find and repair the constant barrage of DNA damage brought on by ultraviolet light radiation and other sources. In a new study NYU School of Medicine researchers reveal how an enzyme called RNA polymerase patrols the genome for DNA damage and helps recruit partners to repair it. The result: fewer mutations and consequently less cancer and other kinds of disease.

The study, led by Evgeny Nudler, PhD, a Howard Hughes Medical Investigator and the Julie Wilson Anderson Professor of Biochemistry at NYU Langone Medical Center, is being published online in the January 8 issue of Nature.

Scientists have long known that RNA polymerase slides along the telltale tracks of double-stranded DNA and uses that template to create a growing chain of RNA molecules. This RNA chain, in turn, contains all of the information needed to construct cellular proteins. The enzyme, however, can stall as it patrols the tracks and encounters significant DNA damage. Even worse, it can become lodged over the damaged site, preventing any repair specialists from reaching it.

In the new study, the NYU School of Medicine researchers reveal how another enzyme called UvrD helicase acts like a train engine to pull the RNA polymerase backwards and expose the broken DNA so a repair crew can get to work.

The finding has major implications for a patching mechanism that is widely shared by organisms ranging from bacteria to humans, says Dr. Nudler. "Better repair means fewer mutations, which also means slower aging, less cancer and many other pathologies," he says.

Although the research, conducted in Escherichia coli bacteria, focused on one type of DNA repair, Dr. Nudler says the evidence suggests that other cellular repair pathways might use the same mechanism to recognize and then resolve the damage. Failure to do so can lead to profound consequences: inherited defects in the gene that encodes the human analog of UvrD, a protein known as XPB, have been linked to a range of devastating disorders.

In a condition known as xeroderma pigmentosum, for example, the faulty DNA repair system cannot fix damage caused by ultraviolet radiation. Consequently, any exposure to sunlight can cause serious skin and eye damage and greatly elevate the risk of skin cancer Similarly, children born with Cockayne syndrome age prematurely and are often short in stature due to inadequate DNA repair. Those with a third related condition called trichothiodystrophy have brittle hair, recurrent infections and delayed development.

The study by Dr. Nudler's group and colleagues in Russia used a battery of biochemical and genetic experiments to directly link UvrD to RNA polymerase and to demonstrate that UvrD's pulling activity is essential for DNA repair. The lab results also suggest that UvrD relies on a second factor, called NusA, to help it pull RNA polymerase backwards. Those two partners then recruit a repair crew of other proteins to patch up the exposed DNA tracks before the train-like polymerase continues on its way.

According to Dr. Nudler, his team's study offers a convincing justification for a puzzling phenomenon known as pervasive transcription, which he calls "one of the most enigmatic and debated subjects of molecular biology." The question, he says, boils down to this: Why do RNA polymerases transcribe most of the genome within humans and other organisms, converting vast stretches of DNA to RNA, when only a tiny fraction of those resulting RNA transcripts will ever prove useful? Isn't that RNA polymerase activity a waste of energy and resources?

"Our results imply that a major role of RNA polymerase is to patrol the genome for DNA damage," he says. "This is the only molecular machine that is capable of continuously scanning the chromosomes for virtually any deviation from the canonical four bases in the template strand: A, T, G and C." The polymerase's extensive transcription activity, then, might be well worth the effort if its continuous vigilance also ensures that any DNA damage gets fixed through the assistance of the pulling factors and other collaborators.

In addition to its insights on DNA repair, the paper describes a powerful new method for mapping protein-protein interactions at high resolution. Dr. Nudler says the method, known as chemical cross-linking coupled with mass-spectrometry, or XLMS, can be widely used by other labs and applied to virtually any protein interactions.


Story Source:

The above story is based on materials provided by NYU Langone Medical Center / New York University School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Vitaly Epshtein, Venu Kamarthapu, Katelyn McGary, Vladimir Svetlov, Beatrix Ueberheide, Sergey Proshkin, Alexander Mironov, Evgeny Nudler. UvrD facilitates DNA repair by pulling RNA polymerase backwards. Nature, 2014; DOI: 10.1038/nature12928

Cite This Page:

NYU Langone Medical Center / New York University School of Medicine. "Molecular engines star in new model of DNA repair." ScienceDaily. ScienceDaily, 8 January 2014. <www.sciencedaily.com/releases/2014/01/140108133305.htm>.
NYU Langone Medical Center / New York University School of Medicine. (2014, January 8). Molecular engines star in new model of DNA repair. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2014/01/140108133305.htm
NYU Langone Medical Center / New York University School of Medicine. "Molecular engines star in new model of DNA repair." ScienceDaily. www.sciencedaily.com/releases/2014/01/140108133305.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Can Watching TV Make You Feel Like A Failure?

Can Watching TV Make You Feel Like A Failure?

Newsy (July 24, 2014) A study by German researchers claims watching TV while you're stressed out can make you feel guilty and like a failure. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile: iPhone Android Web
          Follow: Facebook Twitter Google+
          Subscribe: RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins