Navigation Links
New findings regarding DNA damage checkpoint mechanism in oxidative stress
Date:6/14/2013

In current health lore, antioxidants are all the rage, as "everybody knows" that reducing the amount of "reactive oxygen species" -- cell-damaging molecules that are byproducts of cellular metabolism -- is critical to staying healthy. What everyone doesn't know is that our bodies already have a complex set of processes built into our cells that handle these harmful byproducts of living and repair the damage they cause.

For example, few of us realize that, while our cells' DNA is constantly being damaged by reactive oxygen species (as well as by other forces), there are also complex mechanisms that constantly assess that damage and make repairs to our fragile genetic material at least 10,000 times a day in every cell in our bodies. The vital biochemical processes by which this constant DNA repair takes place are still only partially understood because of their complexity, speed, and the difficulty of studying complex interactions within living cells. Moreover, it remains unknown how cells sense the oxidatively damaged DNA in the first place.

In an article published in the Proceedings of the National Academy of Sciences (PNAS) a research team from University of North Carolina at Charlotte announced that they had uncovered a previously unknown surveillance mechanism, known as a DNA damage checkpoint, used by cells to monitor oxidatively damaged DNA. The finding, first-authored by UNC Charlotte biology graduate student Jeremy Willis and undergraduate honors student Yogin Patel, was also co-authored by undergraduate honors student Barry L. Lentz and assistant professor of biology Shan Yan.

"DNA damage is the underlying pathology in many major human diseases, including cancers and neurodegenerative disorders such as Alzheimer's and Parkinson's, so arriving at a full understanding of the sophisticated mechanisms that cells usually employ to avoid such disastrous outcomes is important," Yan noted.

Two biochemical pathways, known as ATM-Chk2 and ATR-Chk1, govern the cell's response and repair of double-strand DNA breaks and other types of DNA damage or replication stress respectively. The molecular mechanisms underlying the ATR-Chk1 checkpoint activation include the uncoupling of DNA helicase and polymerase activities and DNA end resection of double-strand breaks.

"The significance of what we have found is that there is a third, previously unknown trigger for ATR-Chk1 checkpoint pathway, and this novel mechanism is discovered in the context of oxidative stress," Yan said.

In particular, Yan's team discovered that under conditions of oxidative stress (in the presence of hydrogen peroxide) a base excision repair protein known as APE2 plays unexpected roles in the checkpoint response: single-strand DNA generation and Chk1 association. The protein was previously known to be involved in the DNA repair of oxidative damage, but not to extent revealed in the study's findings. The distinct role of APE2 in the single-strand DNA generation in 3' to 5' direction is referred to as single-strand break end resection ("SSB end resection") by the authors.

The study involved experiments performed with Xenopus laves (the African clawed frog, a species commonly used as a lab animal) egg extracts an experimental system that Yan's lab has developed for studying DNA repair and checkpoint mechanisms in a cell-free conditions. Xenopus is useful because it is a vertebrate (and thus quite similar to humans in cell biology), and its egg cells can be easily produced and manipulated.

Yan is hopeful that this research will open new avenues to pharmacological strategies in drug development for cancer and neurodegenerative diseases.


'/>"/>

Contact: James Hathaway
jbhathaw@uncc.edu
704-687-5743
University of North Carolina at Charlotte
Source:Eurekalert

Related medicine news :

1. New findings in breast cancer
2. Kessler Foundation scientists present cognitive research findings at MS dual symposium
3. Researchers present new findings for novel pancreatic cancer vaccine
4. Mayo Clinic urologists present findings at American Urological Association Annual Meeting
5. Once-Banned Bird Flu Study Yields Sobering Findings
6. Columbus Allergist Dr. Summit Shah Discusses Recent Findings on Food Allergies and Exercise-Induced Anaphylaxis
7. Relief for Migraine Sufferers as The Life House Offers New Findings, Free Consults
8. New findings by GW researcher break tanning misconceptions: There is no such thing as a safe tan
9. MRI findings shed light on multiple sclerosis
10. Unexpected findings at multi-detector CT scans: Less reason to worry
11. New findings on mens genes could alter interpretation of PSA test
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... Little Rock, AR (PRWEB) , ... October 13, ... ... owned firm with locations throughout Arkansas that offers insurance and financial preparation services, ... to benefit the Rock City Rescue organization. , Rock City Rescue is a ...
(Date:10/13/2017)... , ... October 13, 2017 , ... While it’s often ... a problem. Fortunately, an inventor from Austin, Texas, has identified a solution. , She ... in darkness or restricted lighting. As such, it eliminates the need to turn on ...
(Date:10/13/2017)... ... October 13, 2017 , ... The International Association of ... of excellence for the field of eating disorders, announces the opening of early ... in Orlando, Florida at the Omni Resort at ChampionsGate. , The ...
(Date:10/13/2017)... ... October 13, 2017 , ... ... ‘17, and Jennifer Huggins, PharmD ’17, along with clinical associate professor Janice ... of cardiovascular diseases during the 15th Annual Women’s Health Conference. The SIU ...
(Date:10/13/2017)... ... , ... Apple Rehab Shelton Lakes , which specializes in the delivery ... as part of a disaster drill on October 3rd. , Apple Rehab participated with ... Manager, as well as the Connecticut Long Term Care Mutual Aid Plan (LTC-MAP). ...
Breaking Medicine News(10 mins):
(Date:9/28/2017)... Cohen Veterans Bioscience and Early Signal Foundation announce a ... sensors for real-time monitoring of patients with trauma-related and ... focused on disruptive health solutions for rare disorders and ... record and integrate behavioral, cognitive, physiological and contextual data. ... ...
(Date:9/25/2017)... AMSTERDAM , Sept. 25, 2017   ... Trial Master File solutions, today—from the IQPC Trial ... Amsterdam , NL)—announced that EastHORN Clinical Services ... its clinical programs and TMF management. EastHORN, a ... Montrium,s eTMF platform to increase transparency to enable ...
(Date:9/22/2017)... ROCKVILLE, Md. , Sept. 22, 2017  As ... by Republican Senators Bill Cassidy (R-LA) and ... Kalorama Information notes that the medical device industry is ... the medical device tax, the 2.3% excise tax on ... Act.  But they also want covered patients, increased visits ...
Breaking Medicine Technology: