Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

'Sloppier copier' surprisingly efficient

17.07.2009
Article in Nature solves 3 major puzzles about the workings of a famous enzyme involved in DNA repair

The "sloppier copier" discovered by USC biologists is also the best sixth man in the DNA repair game, an article in the journal Nature shows.

The enzyme known as DNA polymerase V (pol V) comes in when a cell's DNA is reeling from radiation damage or other serious blows. Pol V copies the damaged DNA as best it can – saving the life of the bacterial cell at the cost of adding hundreds of random mutations.

The July 16 Nature study reveals pol V's key attributes: economy of motion and quickness to engage.

The study also solves two other stubborn mysteries about the mechanics of DNA repair: the exact composition of the active form of pol V and the crucial role of a protein filament, known as RecA*, that is always present around DNA repair sites, but was never shown to be directly involved.

The three findings together describe an exquisitely efficient process.

"It's a beautiful mechanism for how cells conserve energy," said first author Qingfei Jiang, a graduate student of senior author Myron Goodman, professor of biological sciences and chemistry at USC College.

Cells multiply by division, which starts with the copying of DNA. Pol V kicks in when a section of damaged DNA baffles the enzymes normally involved in copying.

In experiments with E. coli, Jiang and Goodman showed that the activation signal for pol V is the transfer to the enzyme of two key molecules from RecA*.

RecA* is a nucleoprotein filament: a long line of proteins bound to single-stranded DNA. The molecules that RecA* transfers to pol V are ATP, the energy factory of the cell, and a single RecA* protein among the many that make up the filament.

The copying of damaged DNA is formally called "translesion synthesis," or TLS.

"What is RecA* doing?" had been a vexing question in the field for two decades, since the discovery that the filament was necessary for DNA repair. No one, however, could figure out why.

Goodman's group showed that the role of RecA* is limited but direct: It is needed to donate molecules to activate pol V, but it does not participate in damage-induced DNA copying and does not even need to be next to the repair site.

Instead, RecA* acts as a fuel station to put pol V to action.

With the two extra molecules attached, pol V copies the damaged DNA. As soon as it reaches the end of the damaged section, it falls off and immediately deactivates.

Pol V then waits to be called again.

In addition to saving energy, the process prevents the mistake-prone copier from trying to "repair" normal DNA.

"All the other DNA polymerases [enzymes], when they copy DNA, they go first from one and then to another DNA and copy it. Not this baby. It has to be reactivated," Goodman said.

"It's a utility player. It's the guy who does the tough jobs."

He added that the discovery "explains one of the key ways that you get mutations when you damage DNA."

Human cells use similar enzymes, Goodman said.

The study of mutations holds fundamental relevance for medicine, evolutionary biology, aging research and other fields.

Goodman's research group discovered pol V in 1999. The "sloppier copier" nickname, coined by USC science writer Eric Mankin, has since been adopted widely.

At the time, Goodman described pol V as a "last-ditch cell defense" that averts death at the cost of frequent copying mistakes, which show up as mutations in the cell's DNA.

Ironically, the sloppier copier may do more for the long-term success of the species than its accurate cousins. Some of the accidental mutations are likely to be helpful. Cells with those mutations will adapt better to their environment, and the mutations will spread through the species by natural selection.

Goodman and Jiang's co-authors were Kiyonobu Karata and Roger Woodgate of the National Institute of Child Health and Human Development, and Michael Cox of the University of Wisconsin-Madison.

The National Institutes of Health funded the research.

Carl Marziali | EurekAlert!
Further information:
http://www.usc.edu

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>