Navigation Links
Team solves mystery associated with DNA repair

CHAMPAIGN, lll. 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.


Contact: Diana Yates
University of Illinois at Urbana-Champaign

Related medicine news :

1. Solving a biological mystery
2. Cell death mystery yields new suspect for cancer drug development
3. Danish scientists solve old blood mystery
4. Solving the Medical Mystery of Cold Feet
5. Solving the mystery of how cigarette smoking weakens bones
6. 50-year cholera mystery solved
7. Mystery of the missing breast cancer genes
8. Scientists solving the mystery of human consciousness
9. Cleveland Clinic researcher identifies 2 new genetic mutations associated with Cowden syndrome
10. Study suggests vision insurance associated with eye-care visits, better reported vision
11. Pitt research sheds new light on virus associated with developmental delays and deafness
Post Your Comments:
Related Image:
Team solves mystery associated with DNA repair
(Date:6/26/2016)... ... June 26, 2016 , ... Many women ... diagnosed with endometriosis. These women need a treatment plan to not only alleviate ... that can help for preservation of fertility and ultimately achieving a pregnancy. The ...
(Date:6/25/2016)... ... , ... First Choice Emergency Room , the largest network of independent ... Director of its new Mesquite-Samuell Farm facility. , “We are pleased to announce ... Dr. James M. Muzzarelli, Executive Medical Director of First Choice Emergency Room. , ...
(Date:6/24/2016)... Angeles, CA (PRWEB) , ... June 24, 2016 , ... ... surgery procedures that most people are unfamiliar with. The article goes on to state ... procedures, but also many of these less common operations such as calf and cheek ...
(Date:6/24/2016)... ... , ... Global law firm Greenberg Traurig, P.A. announced that 20 Florida attorneys ... peers for this recognition are considered among the top 2 percent of lawyers practicing ... members of this year’s Legal Elite Hall of Fame: Miami Shareholders Mark D. ...
(Date:6/24/2016)... ... June 24, 2016 , ... ... Clinical Decision Making in Emergency Medicine conference in Ponte Vedra Beach, FL. The ... published in Emergency Medicine Practice and Pediatric Emergency Medicine Practice. , ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016 According ... by Type (Standard Pen Needles, Safety Pen Needles), Needle ... GLP-1, Growth Hormone), Mode of Purchase (Retail, Non-Retail) - ... This report studies the market for the forecast period ... reach USD 2.81 Billion by 2021 from USD 1.65 ...
(Date:6/24/2016)... Belgium , June 24, 2016 ... the appointment of Dr. Edward Futcher ... Non-Executive Director, effective June 23, 2016.Dr. Futcher was ... Nominations and Governance Committees.  As a non-executive member ... independent expertise and strategic counsel to VolitionRx in ...
(Date:6/23/2016)... 23, 2016  MedSource announced today that it ... software solution of choice.  This latest decision demonstrates ... to their clients by offering a state-of-the-art electronic ... establishes nowEDC as the EDC platform of choice ... clients.  "nowEDC has long been a preferred EDC ...
Breaking Medicine Technology: