Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists Use X-Ray Vision to Probe Early Stages of DNA 'Photocopying'

12.03.2015

Finding: Protein complex isn't always "on."

Scientists at Johns Hopkins have created a 3-D model of a complex protein machine, ORC, which helps prepare DNA to be duplicated. Like an image of a criminal suspect, the intricate model of ORC has helped build a “profile” of the activities of this crucial “protein of interest.”


Fraziska Bleichert, James Berger, Johns Hopkins Medicine

A simplified model of the ORC protein machine shows where DNA fits (asterisk) and where the Orc6 piece attaches (triangle).

But the new information has uncovered another mystery: ORC’s structure reveals that it is not always “on” as was previously thought, and no one knows how it turns on and off.

A summary of the study will be published in the journal Nature on March 11.

... more about:
»3-D »DNA »MCM »ORC »crystals »inside »protein complex »strands

“Even though the ORC protein machinery is crucial to life, we didn’t know much about how it works,” says James Berger, Ph.D., professor of biophysics and biophysical chemistry. “By learning what it looks like, down to the arrangement of each atom, we can get a sense of where it interacts with DNA and how it does its job.”

Multicelled organisms grow when their cells divide into two. However, before a cell can divide, it has to make copies of its parts for the new cell. Since DNA's information is sealed inside its double strands, a specialized machine, called the replisome, must unseal the strands before the information can be accessed and copied.

A key piece of the replisome is a motor, termed MCM, which unwinds paired DNA strands. MCM is a closed protein ring that must be opened up before it can encircle the long strands of DNA. ORC, the origin recognition complex, solves that problem. It cracks open the MCM's circle so that it can fit around the DNA and unwind it.

It was previously known that ORC is a six-piece protein complex, with five of the pieces forming a slightly opened ring and the sixth, Orc6, forming a tail. Mistakes in Orc6 cause assembly problems, which affect the function of the whole machine and contribute to a dwarfism disorder called Meier-Gorlin syndrome.

To learn more about how the complex works, Franziska Bleichert, Ph.D., a postdoctoral fellow in Berger’s laboratory, extracted the protein from fruit fly cells and immobilized it by coaxing it into tiny crystals. She then analyzed its structure by shining high-energy X-rays at the crystals in very focused beams. The resulting data allowed her to reconstruct the precise shape of the proteins, atom by atom, on the scale of billionths of an inch.

Her model reveals exactly where Orc6 connects to the ring of ORC and explains how mistakes in that protein wreak havoc, though why dysfunctional ORC should cause dwarfism is still a mystery.

The 3-D model also showed the existence of an unexpected regulatory mechanism. It was previously thought that ORC was always “on,” just not always present in the nucleus where it does its work. The model shows that it can exist in an inactive state, raising the question: How does it turn on and off?

“In hindsight, it’s not surprising that there is another level of regulation for ORC,” explains Berger. For example, he says, “As soon as an egg cell is fertilized, it has to jump into action to create the embryo through multiple rounds of cell division, which first requires DNA replication. This inactive state might allow egg cells to stockpile ORC inside the nucleus so it’s available when needed." His team plans to test this idea soon.

Michael Botchan of the University of California, Berkeley, also contributed to the research.

This work was supported by grants from the National Institute of General Medical Sciences (GM071747), the National Cancer Institute (CA R37-30490) and the University of California, Berkeley, Miller Institute for Basic Research in Science.

Contact Information
Catherine Kolf
Senior Communications Specialist
ckolf@jhmi.edu
Phone: 443-287-2251
Mobile: 443-440-1929

Catherine Kolf | newswise
Further information:
http://www.jhmi.edu

Further reports about: 3-D DNA MCM ORC crystals inside protein complex strands

More articles from Life Sciences:

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

nachricht The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

InLight study: insights into chemical processes using light

05.12.2016 | Materials Sciences

High-precision magnetic field sensing

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>