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 Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

nachricht Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Molecular switch will facilitate the development of pioneering electro-optical devices

24.05.2018 | Power and Electrical Engineering

Research reveals how order first appears in liquid crystals

23.05.2018 | Life Sciences

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>