Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Research in yeast yields missing link in DNA maintenance machinery


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:

More articles from Life Sciences:

nachricht Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute

nachricht 'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

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

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

More VideoLinks >>>