Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Guardian of the genome, role for ATR revealed


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:

More articles from Life Sciences:

nachricht ‘Farming’ bacteria to boost growth in the oceans
24.10.2016 | Max-Planck-Institut für marine Mikrobiologie

nachricht Calcium Induces Chronic Lung Infections
24.10.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

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

Oasis of life in the ice-covered central Arctic

24.10.2016 | Earth Sciences

‘Farming’ bacteria to boost growth in the oceans

24.10.2016 | Life Sciences

Light-driven atomic rotations excite magnetic waves

24.10.2016 | Physics and Astronomy

More VideoLinks >>>