Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Guardian of the genome, role for ATR revealed

03.03.2003


In order for the body to grow, reproduce and remain cancer free, the cells of the body must have a mechanism for both detecting DNA damage and a feedback mechanism for telling the rest of the cell’s machinery to stop what it’s doing until the damage may be fixed. This feedback mechanism relies on checkpoints during different stages of the cell’s division cycle. Eric Brown and David Baltimore at the California Institute of Technology (Pasadena, CA) have now further defined how the ATR kinase participates in this feedback mechanism as a member of the DNA damage checkpoint machinery. Their study, which appears in the March 1st issue of Genes & Development, utilizes a novel mouse model to produce mouse cells that lack the ATR kinase. The ATR deficient cells have major defects in cell cycle checkpoint regulation and halting the cell cycle. These mouse cells proceed dangerously through the cell division cycle with chromosome breaks, demonstrating a role for ATR in maintaining the integrity of DNA.



ATR, and a similar protein ATM, have previously been shown to be involved in the response to DNA damage. However previous experiments to determine the role of ATR in preventing cells with damaged DNA from dividing have been contradictory and the precise roles of these proteins have remained obscure. The previous attempts to determine the role of ATR were hindered by the inviability of ATR deficient mice. In this report, the authors use a clever modification of the mouse knockout technology to create cells that can be forced to lose the ATR gene at will.

Cells lacking ATR and ATM did not properly halt the cell division cycle in response to ionizing radiation, a potent DNA damage-inducing agent. Both ATR and ATM contributed to the checkpoint control soon after DNA damage, but ATR was responsible for regulating the control later in the cell cycle. ATR was also important for regulating a checkpoint signaling pathway previously described in yeast that is initiated by stalled DNA replication. Surprisingly though, ATR was not essential for cell cycle arrest in response to incomplete DNA replication, implying that an additional mechanism must be a work. Brown & Baltimore go on to show that when ATR is absent, inhibited DNA replication causes the formation of a very serious form of damage known as double strand breaks. This suggests that while ATR is dispensable for the cell cycle delay in response to incomplete DNA replication, it is essential for ensuring the cells leaving this delay are free of DNA damage.


This study shows that ATR plays an important role in the maintenance of genome integrity. Without this important guardian, cells ignore DNA damage, replicate the unrepaired chromosomes and pass on damaged DNA. Ultimately, this DNA damage could lead to a loss of cell function, cellular death and diseases such as cancer. Consistent with the later, previous work from Brown and Baltimore (2000), showed that even partial loss of ATR function can lead to increased incidence of late-onset cancer in mice.

"It is a very exciting time for the DNA damage response field. Everywhere you look in these pathways, connections can be made to how cancer is normally prevented by maintaining the integrity of the genome. Subtle, yet-to-be-determined deficiencies in any of a number of these DNA damage response molecules may broadly influence cancer risk in humans," explains Dr. Brown.

Michele McDonough | EurekAlert!
Further information:
http://www.cshl.org/

More articles from Life Sciences:

nachricht Antimicrobial substances identified in Komodo dragon blood
23.02.2017 | American Chemical Society

nachricht New Mechanisms of Gene Inactivation may prevent Aging and Cancer
23.02.2017 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

From rocks in Colorado, evidence of a 'chaotic solar system'

23.02.2017 | Physics and Astronomy

'Quartz' crystals at the Earth's core power its magnetic field

23.02.2017 | Earth Sciences

Antimicrobial substances identified in Komodo dragon blood

23.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>