Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genome-wide screen reveals new tricks of old genes

23.04.2004


Process shows how mounds of data can be effectively managed



Johns Hopkins scientists have successfully used new techniques to search the yeast genome for genes that help keep copied chromosomes together, protecting the integrity of the organism’s genetic material during cell division.

By combining two genome-wide screens, the researchers were able to narrow down the dozens of genes identified by the first screen to just 17 that made both cut-offs -- a number small enough to be cost- and time-efficient to consider in some detail. Their report appears in the April issue of Molecular Biology of the Cell.


"Data created from new genome-scanning techniques can be overwhelming. Reading all there is to know about 50 genes to figure out what new knowledge may be lurking in the haystack is very difficult," says Forrest Spencer, Ph.D., associate professor in Hopkins’ McKusick-Nathans Institute of Genetic Medicine. "But by overlapping information from two screens, we were able to figure out what Mother Nature was trying to tell us that wasn’t too complicated for us to understand."

While the researchers had hoped their screens would reveal new genes and their functions, they instead identified genes previously linked to two other aspects of shepherding genetic material during cell division. Fifteen of the highlighted genes were already known to help ensure the accuracy of copied DNA and two help move chromosomes to opposite ends of the dividing cell.

But the researchers’ results give these "old" genes new jobs, associating them with cohesion, the little-understood process of keeping a chromosome and its copy together until the cell is ready to split in two. If the "sister" chromosomes aren’t kept together, both copies could end up on one side of the dividing cell. Another problem is that the copies could undergo extra rearrangements, risking loss of important genes.

"If there’s no cohesion, the cell will die," says Spencer. "However, if the process sometimes works and sometimes doesn’t, some cells survive but their genetic material gets scrambled."

It’s that sometimes-yes-sometimes-no problem that Spencer and her team are trying to figure out, in part because it’s interesting biology, but also because genetic instability plays such a big role in the development of cancer in humans. No one knows exactly at what point errors enter the genetic material and aren’t fixed, but the intricacies of chromosomes’ manipulation during cell division seem a good place to start.

Postdoctoral fellow Cheryl Warren, Ph.D., started the search by screening 5,916 yeast genes -- all at once -- for ones needed for survival in the absence of a gene called ctf4, already known to be a critical component of cohesion. Twenty-six genes popped out of this screen, a type known as "synthetic lethal" since the yeast survive the loss of either one, but not both, genes.

However, the synthetic lethal effect of some, if not many, of the genes from this screen would be due to problems other than faulty cohesion, the researchers knew. "We had to do something else to get a manageable starting point," says Warren.

So, using a technique she developed to identify whether a gene’s loss causes the genetic material to become scrambled, Warren tested those 26 genes to see which of them seemed most likely to contribute to genetic instability through their involvement in cohesion. In these experiments, markers were scattered throughout the yeast’s genetic material so she could easily tell if pieces of the genome moved or went missing when a gene was knocked out.

Only 17 of the 26 identified genes caused genetic instability when missing from the yeast genome. Fifteen of those genes are involved in double-checking whether newly formed strands of DNA matched the cell’s original genetic material and calling in "repairmen" as needed (a process called the "S-phase checkpoint"). The other two genes are part of the machinery previously known to help move the two sets of chromosomes to opposite sides of the dividing cell.

"By using both screens, we got a number that was small enough to follow-up on, and yet large enough to reveal a trend," says Warren. "This is the first evidence that proteins involved in checking the DNA sequence are also involved in keeping sister chromosomes together, and it’s a great starting point for understanding more."


The research was funded by the National Human Genome Research Institute, the National Institute for General Medical Sciences, and the National Heart, Lung, and Blood Institute, all components of the National Institutes of Health.

Authors on the report are Warren, Spencer, Mark Eckley, Marina Lee, Joseph Hanna, Adam Hughes, Brian Peyser and Chunfa Jie of the McKusick-Nathans Institute; and Rafael Irizarry of the Johns Hopkins Bloomberg School of Public Health.

Joanna Downer | EurekAlert!
Further information:
http://www.hopkinsmedicine.org/
http://www.molbiolcell.org/cgi/reprint/E03-09-0637v1.pdf

More articles from Life Sciences:

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

nachricht Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

NASA's Fermi catches gamma-ray flashes from tropical storms

25.04.2017 | Physics and Astronomy

Researchers invent process to make sustainable rubber, plastics

25.04.2017 | Materials Sciences

Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017

25.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>