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 cells machinery to stop what its doing until the damage may be fixed. This feedback mechanism relies on checkpoints during different stages of the cells 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.
Michele McDonough | EurekAlert!
More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy