Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How yeast chromosomes avoid the bad breaks

08.08.2011
The human genome is peppered with repeated DNA elements that can vary from a few to thousands of consecutive copies of the same sequence.

During meiosis—the cell division that produces sperm and eggs—repetitive elements place the genome at risk for dangerous rearrangements from genome reshuffling. This recombination typically does not occur in repetitive DNA, in part because much of it is assembled into specialized heterochromatin. Other mechanisms that restrain recombination in repetitive DNA have remained elusive, until now.

In a paper published online today in the journal Nature, researchers in the lab of Whitehead Institute Fellow Andreas Hochwagen describe a defense mechanism in yeast that shields repetitive DNA from meiotic DNA recombination. According to the work of Hochwagen and his colleagues, the protective repeat-associated heterochromatin makes the DNA segments near the boundary of the heterochromatin particularly vulnerable to inappropriate meiotic recombination. DNA elements surrounding these at-risk border regions are protected from meiotic recombination by a novel system involving the concerted action of two proteins, pachytene checkpoint protein 2 (Pch2) and origin recognition complex subunit 1 (Orc1), which are present in organisms ranging from yeast to humans.

During meiosis an organism's chromosomes pair up, with every pair containing a copy inherited from each of the organism's parents. To match up the chromosomes, the cell breaks both strands of the chromosomes' DNA in multiple locations, and the chromosomes swap DNA sections that have the same sequence. Later, when the paired chromosomes are pulled apart, each resulting chromosome is a patchwork of maternal and paternal genes. The creation of reshuffled chromosomes assists chromosome assortment into spore, sperm, and egg cells, but it also has a profound effect on evolution, because it produces new genetic variants.

"To me it's always been very confusing why you would break your genome. It's your blueprint," says Hochwagen. "Obviously, it helps you make new variations and combinations of genes, but it's incredibly dangerous and you really need to make sure that it happens the right way."

In repetitive DNA, this system of breaking and swapping is particularly hazardous, as there are many options that a section of repeat DNA could be swapped with. If the wrong repeat is chosen, a chromosome can gain or lose a large chunk of DNA. In humans, such mistakes have been linked to genetic neurological and developmental disorders, including autism spectrum disorders and schizophrenia.

By studying the highly repetitive DNA that makes up yeast's ribosomal DNA (rDNA), Gerben Vader and Hannah Blitzblau, first authors of the Nature paper and postdoctoral researchers in Hochwagen's lab, have determined that yeast's rDNA is protected from inappropriate recombination by two mechanisms. It was previously shown that heterochromatin prevents chromosome breakage in repetitive DNA. But in their paper, Vader and Blitzblau demonstrate that, ironically, the protective heterochromatin renders the transition zone between the repetitive and non-repetitive DNA particularly fragile. The yeast cell buttresses these borders with Pch2 and Orc1, which prevent chromosome breakage across the entire transition zone. In their absence, rDNA frequently gains or loses repeats.

"We had previously seen very little chromosome breakage in large regions close to repetitive DNA," says Blitzblau. "The finding that the borders of heterochromatin are particularly fragile helps us to understand why the cell invests in specifically protecting these regions."

Although the modes of heterochromatin formation vary between organisms, similar strategies may be at work in higher organisms, too.

"In mice and flies repetitive DNA is also packaged into heterochromatin, and there is evidence that very few breaks happen in these regions during meiosis," says Vader. "So it is possible that this type of protection is a general phenomenon."

This research was supported by the National Institutes of Health (NIH), the Netherlands Organization for Scientific Research, and Howard Hughes Medical Institute (HHMI).

Andreas Hochwagen's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted.

Full Citations:

"Protection of repetitive DNA borders from self-induced meiotic instability"
Nature, online August 7, 2011.
Gerben Vader (1*), Hannah G. Blitzblau (1*), Mihoko A. Tame (1), Jill E. Falk (1,3), Lisa Curtin (1,2) and Andreas Hochwagen (1).
1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
2. Somerville High School, Somerville, Massachusetts 02143, USA.
3. Present address: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

* These authors contributed equally to this work

Nicole Giese | EurekAlert!
Further information:
http://www.wi.mit.edu

More articles from Life Sciences:

nachricht Bacteria as pacemaker for the intestine
22.11.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Researchers identify how bacterium survives in oxygen-poor environments
22.11.2017 | Columbia 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: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Corporate coworking as a driver of innovation

22.11.2017 | Business and Finance

PPPL scientists deliver new high-resolution diagnostic to national laser facility

22.11.2017 | Physics and Astronomy

Quantum optics allows us to abandon expensive lasers in spectroscopy

22.11.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>