Navigation Links
Novel connection found between biological clock and cancer

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.


'"/>

Source:Dartmouth Medical School


Related biology news :

1. Novel Asthma Study Shows Multiple Genetic Input Required; Single-gene Solution Shot Down
2. Novel technology detects human DNA mutations
3. Novel antiviral technology inhibits RSV infection in mice
4. Novel Enzyme Shows Potential As An Anti-HIV Target
5. Novel Therapy Tested in Mice Could Chase Away Cat Allergies
6. Discovery Could Lead To Novel Approaches In HIV Treatment
7. Novel ultrafast laser detection of cancer cells also may improve understanding of stem cells
8. Research Using Mouse Models Reveals A Novel Key Player In The Initiation Of Colon Cancer
9. Novel gene-silencing nanoparticles shown to inhibit Ewings sarcoma
10. Novel live reporting system to track cells
11. Field of beams - Novel system uses polarized light pulses to reveal crop health
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:5/9/2016)... , UAE, May 9, 2016 ... it comes to expanding freedom for high net worth ... Even in today,s globally connected world, there is still ... system could ever duplicate sealing your deal with a ... second passports by taking advantage of citizenship via investment ...
(Date:4/26/2016)... and LONDON , April ... part of EdgeVerve Systems, a product subsidiary of ... today announced a partnership to integrate the Onegini ...      (Logo: http://photos.prnewswire.com/prnh/20151104/283829LOGO ) ... their customers enhanced security to access and transact ...
(Date:4/15/2016)... April 15, 2016 Research ... Gait Biometrics Market 2016-2020,"  report to their offering.  ... ) , ,The global gait biometrics market is ... during the period 2016-2020. Gait analysis ... can be used to compute factors that are ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... 2016 , ... Parallel 6 , the leading software as a service ... Virtual Patient Encounter CONSULT module which enables both audio and video telemedicine communication ... , Using the CONSULT module, patients and physicians can schedule a face to face ...
(Date:6/24/2016)... -- Regular discussions on a range of subjects including policies, debt ... said Poloz. Speaking at a lecture to the ... pointed to the country,s inflation target, which is set by ... "In certain areas there needs to ... goals, why not sit down and address strategy together?" ...
(Date:6/23/2016)... WI (PRWEB) , ... June 23, 2016 , ... ... supplements, is pleased to announce the launch of their brand, UP4™ Probiotics, into ... for over 35 years, is proud to add Target to its list of ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... (Yeast and Mold) microbial test has received AOAC Research Institute approval 061601. , ... tests introduced last year,” stated Bob Salter, Vice President of Regulatory and Industrial ...
Breaking Biology Technology: