Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research in yeast yields missing link in DNA maintenance machinery

17.12.2004


In a finding akin to discovering pages missing from an antique car repair manual, researchers from The University of Texas M. D. Anderson Cancer Center have linked for the first time two biological processes crucial to cell survival.

The finding, reported in the Dec. 17, 2004, issue of the journal Cell, provides the first link between a cell’s DNA repair machinery and its DNA storage and retrieval machinery. The two processes have been studied independently, and each is essential for proper care and maintenance of the cell’s genetic material, but until now there was little evidence of how the two might work together.

"We have brought together two fields that are essential for proper maintenance of DNA," said Xuetong "Snow" Shen, assistant professor in the Department of Carcinogenesis at M. D. Anderson. "It was generally understood there must be a connection between the two, but no direct connection had ever been seen. We have bridged that gap."



Many types of cancer, including human leukemias and lymphomas, have been linked to defects in DNA maintenance. Shen’s lab studied a particular protein complex, called INO80, that regulates access to DNA. Inside cells, long strands of DNA are wound tightly around a series of proteins called histones. The combination of DNA and its associated proteins is called chromatin. The histone proteins help compact the DNA and help keep it organized within the chromosome, said Shen, but DNA tightly wound around histones is inaccessible. If DNA becomes damaged by radiation, reactive chemicals or ultraviolet light, for example, it must be repaired. But the bulky repair proteins need to gain access to the damaged areas of DNA. That’s where INO80 chromatin remodeling might comes in. Its role, discovered by Shen and his colleagues, is likely to loosen the damaged DNA from the grip of histone proteins so the DNA repair machinery can access the damaged section. When INO80 is not working properly, damaged DNA can go unrepaired. Such damage can lead to unstable cells and eventually to cancer.

"We knew that at least one gene involved in the INO80 complex had been linked to cancer," said Shen. "This research helps provide a potential mechanism to account for those cancers."

The researchers, led by post-doctoral scientist Ashby Morrison, Ph.D., studied how yeast cells repair double-stranded DNA breaks.

"Double strand breaks are the most serious type of DNA damage," said Shen. "The two DNA strands are completely severed. It is a disaster for a cell. If it is not repaired, the chromosomes become unstable and can fuse to other chromosomes. Many types of cancer result from chromosome fusions."

The scientists created an experimental double strand break in the yeast DNA and monitored specially tagged INO80 molecules inside the cells. They found that INO80 proteins recognize a specific form of histone protein called gamma-H2AX that acts as a "flag" or "code" to direct DNA repair proteins to DNA breaks. Once attached to the histone protein, the INO80 proteins most likely loosen the histone grip on DNA so the repair machinery can gain access and repair the broken ends, the scientists report.

In particular, the scientists discovered one member of the INO80 complex, called Nhp10, is crucial to recognizing the histone code for damaged DNA.

Shen first discovered the INO80 complex in 2000 while studying yeast. Since then, he has revealed that this large protein complex plays an important role in making DNA available for copying into RNA. This latest discovery expands the importance of the INO80 complex, showing it is also crucial to helping repair broken DNA. The scientists discovered that if certain members of the INO80 complex are missing, the yeast becomes prone to the kind of serious damage to its genetic material that can lead to cancer in people. "The INO80 complex is found in organisms from yeast to humans," said Shen. "Typically these kinds of universal proteins play important basic biological functions, and that is turning out to be the case here."

The scientists are now working out the precise role that INO80 plays in DNA repair and what the protein complex does to the chromosome structure at the double strand break. "We have introduced a whole new player that has never been seen before in double-strand break repair," said Shen. "This is only the beginning."

In addition to Shen and Morrison, technician Jessica Highland from M. D. Anderson; Nevan Krogan and Jack Greenblatt, Ph.D., University of Toronto; and Ayelet Arbel-Eden and James Haber, Ph.D., Brandeis University, contributed to the research. The research was funded by grants from the National Institutes of Health and M. D. Anderson Cancer Center.

Julie A. Penne | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society

nachricht 127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>