Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Team solves mystery associated with DNA repair

14.12.2012
Every time a human or bacterial cell divides it first must copy its DNA.

Specialized proteins unzip the intertwined DNA strands while others follow and build new strands, using the originals as templates. Whenever these proteins encounter a break – and there are many – they stop and retreat, allowing a new cast of molecular players to enter the scene.

Scientists have long sought to understand how one of these players, a repair protein known as RecA in bacterial cells, helps broken DNA find a way to bridge the gap. They knew that RecA guided a broken DNA strand to a matching sequence on an adjoining bit of double-stranded DNA, but they didn’t know how. In a new study, researchers report they have identified how the RecA protein does its job.

“The puzzle for scientists has been: How does the damaged DNA look for and find its partner, the matching DNA, so that it can repair itself?” said University of Illinois physics professor Taekjip Ha, who led the study. “Because the genomic DNA is millions of bases long, this task is much like finding a needle in a haystack. We found the answer to how the cell does this so quickly.”

The research is described in a paper in eLife, a new open-access journal supported by the Howard Hughes Medical Institute (HHMI), the Max Planck Society and the Wellcome Trust. Ha is an HHMI investigator. The National Science Foundation provided primary funding for this work.

DNA repair is vital to health, vitality and longevity. Disruptions of the process can lead to the early onset of diseases associated with aging or cancer in animals. The breast cancer mutation known as BRCA2, for example, disrupts a gene involved in loading Rad51 (the human equivalent of RecA) onto a broken DNA strand to begin the process of repair.

Previous studies have shown that in bacteria, RecA forms a filament that winds itself around a broken, single strand of DNA. Like a matchmaker trying to find a partner for an unpaired dancer, it scours the corresponding DNA strands for a sequence that will pair up perfectly with the broken strand.

Once it finds the sequence, the broken strand steps in and chemically bonds to its new partner, displacing one of the unbroken strands (which eventually pairs with the other broken strand). This elaborate molecular square dance allows the cell to go back to the work of duplicating its genome. Each broken strand now is paired with an unbroken one, and uses the intact strand as a template for replication. (Watch an animation about this process.)

“If a break in DNA occurs, you have to repair it,” Ha said. “We wanted to know how RecA helps the DNA find a sequence complementary to it in the sea of genomic DNA, and how it does it so quickly.”

To answer this question, the researchers made use of fluorescence resonance energy transfer (FRET) to observe in real time the interaction of the RecA protein and the DNA. FRET uses fluorescent molecules whose signals vary in intensity depending on their proximity to one another. By labeling a single DNA strand bound by RecA and putting a different fluorescent label on a stretch of double-stranded DNA, the researchers could see how the molecules interacted with one another.

The team determined that RecA that is bound to a broken, single-stranded DNA molecule actually slides back and forth along the double-stranded DNA molecule searching for a match.

“We discovered that this RecA filament can slide on double-stranded DNA for a span of sequences covering about 200 base pairs of DNA,” Ha said. “This is how one strand of DNA can be exchanged with another from a different DNA duplex. That’s the process called ‘recombination.’ ”

The discovery explains how DNA repair can occur so quickly, Ha said.
“We did a calculation that found that without this kind of process that we discovered, then DNA repair would be 200 times slower,” he said. “So your DNA would not be repaired quickly and damage would accumulate, possibly leading to serious diseases.”

The research team included graduate students Kaushik Ragunathan and Cheng Liu. Ha is an affiliate of the Institute for Genomic Biology and a co-director of the NSF Center for the Physics of Living Cells at Illinois.

Editor’s notes: To reach Taekjip Ha, call 217-265-0717; email tjha@illinois.edu.
The paper, “RecA Filament Sliding on DNA Facilitates Homology Search,” is available online: http://elife.elifesciences.org/content/1/e00067

Diana Yates | University of Illinois
Further information:
http://www.illinois.edu

More articles from Life Sciences:

nachricht Protein scaffold
27.05.2015 | Okinawa Institute of Science and Technology (OIST) Graduate University

nachricht Seeing the action
27.05.2015 | University of California - Santa Barbara

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Advance in regenerative medicine

The only professorship in Germany to date, one master's programme, one laboratory with worldwide unique equipment and the corresponding research results: The University of Würzburg is leading in the field of biofabrication.

Paul Dalton is presently the only professor of biofabrication in Germany. About a year ago, the Australian researcher relocated to the Würzburg department for...

Im Focus: Basel Physicists Develop Efficient Method of Signal Transmission from Nanocomponents

Physicists have developed an innovative method that could enable the efficient use of nanocomponents in electronic circuits. To achieve this, they have developed a layout in which a nanocomponent is connected to two electrical conductors, which uncouple the electrical signal in a highly efficient manner. The scientists at the Department of Physics and the Swiss Nanoscience Institute at the University of Basel have published their results in the scientific journal “Nature Communications” together with their colleagues from ETH Zurich.

Electronic components are becoming smaller and smaller. Components measuring just a few nanometers – the size of around ten atoms – are already being produced...

Im Focus: IoT-based Advanced Automobile Parking Navigation System

Development and implementation of an advanced automobile parking navigation platform for parking services

To fulfill the requirements of the industry, PolyU researchers developed the Advanced Automobile Parking Navigation Platform, which includes smart devices,...

Im Focus: First electrical car ferry in the world in operation in Norway now

  • Siemens delivers electric propulsion system and charging stations with lithium-ion batteries charged from hydro power
  • Ferry only uses 150 kilowatt hours (kWh) per route and reduces cost of fuel by 60 percent
  • Milestone on the road to operating emission-free ferries

The world's first electrical car and passenger ferry powered by batteries has entered service in Norway. The ferry only uses 150 kWh per route, which...

Im Focus: Into the ice – RV Polarstern opens the arctic season by setting course for Spitsbergen

On Tuesday, 19 May 2015 the research icebreaker Polarstern will leave its home port in Bremerhaven, setting a course for the Arctic. Led by Dr Ilka Peeken from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) a team of 53 researchers from 11 countries will investigate the effects of climate change in the Arctic, from the surface ice floes down to the seafloor.

RV Polarstern will enter the sea-ice zone north of Spitsbergen. Covering two shallow regions on their way to deeper waters, the scientists on board will focus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International symposium: trends in spatial analysis and modelling for a more sustainable land use

20.05.2015 | Event News

15th conference of the International Association of Colloid and Interface Scientists

18.05.2015 | Event News

EHFG 2015: Securing health in Europe. Balancing priorities, sharing responsibilities

12.05.2015 | Event News

 
Latest News

Technology that feels good

27.05.2015 | Information Technology

A chip placed under the skin for more precise medicine

27.05.2015 | Health and Medicine

Linking superconductivity and structure

27.05.2015 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>