Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel connection found between biological clock and cancer

03.07.2006
Dartmouth Medical School geneticists have discovered that DNA damage resets the cellular circadian clock, suggesting links among circadian timing, the cycle of cell division, and the propensity for cancer.

Their work, reported June 29 in Science Express, the advance electronic publication of Science, implies a protective dimension for the biological clock in addition to its pacemaker functions that play such a sweeping role in the rhythms and activities of life.

"The notion that the clock regulates DNA-damage input and that mutation can affect the clock as well as the cell cycle is novel," says Jay Dunlap, professor and chair of genetics at DMS. "It suggests a fundamental connection among circadian timing, cell cycle progress, and potentially the origins of some cancers."

Dunlap is a co-author of the paper with DMS colleagues, Jennifer Loros, professor of biochemistry, graduate student Christopher L. Baker, and former students António M. Pregueiro and Qiuyun Liu.

The team of Loros and Dunlap were among to first to delineate the intricate web of clockwork genes, proteins and feedback loops that drive circadian rhythms, working chiefly in the classic genetic model organism Neurospora, the common bread mold.

One gene (period-4) was identified over 25 years ago by a mutation that affects two clock properties, shortening the circadian period and altering temperature compensation. For this study, the researchers cloned the gene based on its position in the genome, and found it was an important cell cycle regulator. When they eliminated the gene from the genome, the clock was normal, indicating that the mutation interfered in some way with the clock, rather than supplying something that the clock normally needs to run.

Biochemically, the mutation results in a premature modification of the well understood clock protein, frequency (FRQ). The investigators demonstrated that this was a direct result of action by an enzyme, called in mammals checkpoint kinase-2 (CHK2), whose normal role is exclusively in regulating the cell division cycle. CHK2 physically interacts with FRQ; the mutation makes this interaction much stronger. However, a mutant enzyme that has lost its activity has no effect on the clock.

Normally CHK2 is involved in the signal response pathway that begins when DNA is damaged and results in a temporary stoppage of cell division until the damage is fixed. The researchers found that the resetting effect of DNA damage requires the period-4 clock protein, and that period-4 is the homolog, the Neurospora version, of the mammalian checkpoint kinase.

Moreover, the clock regulates expression of the period-4 gene. This closes a loop connecting the clock to period-4 and period-4 to the clock and the cell cycle. The clock normally modulates expression of this gene that encodes an important cell cycle regulator, and that cell cycle regulator in turn affects not only the cell cycle but also the clock.

Recent evidence in mammalian cells shows that other cell cycle regulators physically interact with clock proteins. Loss of at least one clock protein (mammalian period-2) is known to increase cancer susceptibility. The coordination of the clock and cell division through cell cycle checkpoints, supports the clock's "integral role in basic cell biology," conclude the researchers." Their work can help advance understanding of cancer origins as well as the timing of anti-cancer treatment.

Dartmouth Public Affairs | EurekAlert!
Further information:
http://www.dartmouth.edu/

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Transport of molecular motors into cilia

28.03.2017 | Life Sciences

A novel hybrid UAV that may change the way people operate drones

28.03.2017 | Information Technology

NASA spacecraft investigate clues in radiation belts

28.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>