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 For a chimpanzee, one good turn deserves another
27.06.2017 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)

nachricht New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Touch Displays WAY-AX and WAY-DX by WayCon

27.06.2017 | Power and Electrical Engineering

Drones that drive

27.06.2017 | Information Technology

Ultra-compact phase modulators based on graphene plasmons

27.06.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>