Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

New Findings Regarding DNA Damage Checkpoint Mechanism in Oxidative Stress

Published: Thursday, June 20, 2013
Last Updated: Thursday, June 20, 2013
Bookmark and Share
Scientists uncover previously unknown surveillance mechanism.

In current health lore, antioxidants are well known to reduce 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-stand 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.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,500+ scientific posters on ePosters
  • More than 3,800+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Autism Mutation Isolated – Could Be Treated with Specific Enzyme
The research shows the precise cellular mechanisms that could increase risk for the disorder and how an existing drug might help thousands of people with autism.
Monday, August 10, 2015
New Gene Therapy For Hemophilia Shows Potential As Safe Treatment
Research showed that bleeding events were drastically decreased in animals with hemophilia B. Using a viral vector to swap out faulty genes proved safe and could be used for the more common hemophilia A.
Tuesday, March 17, 2015
Genetically Speaking, Mammals Are More Like Their Fathers
A first of its kind study shows that who we inherit genetic variants from – our mother or father – is crucial for the development of diseases and for research studies aimed at finding causes and potential treatments.
Wednesday, March 04, 2015
Researchers Silence Leading Cancer-Causing Gene
A novel siRNA-based molecule successfully targets KRAS, a well-studied but hard to halt protein important for cancer development and metastasis.
Monday, November 17, 2014
New Gene Therapy Proves Promising as Hemophilia Treatment
Researchers package specialized blood platelets with genes that express clotting factor, leading to fewer bleeding events.
Wednesday, December 18, 2013
Molecular Twist Helps Regulate the Cellular Message to Make Histone Proteins
Researchers show for the first time how two key proteins in messenger RNA communicate via a molecular twist to help maintain the balance of histones to DNA.
Monday, January 21, 2013
Informatics Approach Helps Doctors, Patients Make Sense of Genome Data
Researchers from UNC unveil an analysis framework aimed at helping clinicians spot “medically actionable findings” from genetic tests in an efficient manner.
Friday, September 21, 2012
Molecular Delivery Truck Serves Gene Therapy Cocktail
University of North Carolina scientists have devised a gene therapy cocktail that has the potential to treat some inherited diseases associated with “misfolded” proteins.
Tuesday, August 23, 2011
Clinical Trial of Molecular Therapy for Muscular Dystrophy Yields Significant Positive Results
A molecular technique originally developed at the University of North Carolina at Chapel Hill has taken one step closer to becoming a treatment for the devastating genetic disease Duchenne muscular dystrophy.
Tuesday, July 26, 2011
Structure of 450 Million Year Old Protein Reveals Evolution’s Steps
Researchers have determined the atomic structure of an ancient protein, revealing in detail how genes evolved their functions.
Wednesday, August 22, 2007
Gene Discovered by Researchers Tied to Pancreatic Cancer
The gene, palladin, is involved is involved in the formation of scar tissue on nerve cells in the brain or spinal cord.
Monday, December 18, 2006
Three Lung Tumor Subtypes Identified in DNA Profiling Study
The finding may provide clinical information about patient survival in early- or late-stage disease.
Thursday, November 02, 2006
Studies Find General Mechanism of Cellular Aging
Studies suggest tumor suppressor gene is key.
Friday, September 08, 2006
Novel Enzyme Offers new Look at Gene Regulation
Scientists show that a protein called JHDM1A is able to remove a methyl group from histone H3.
Wednesday, December 28, 2005
Scientific News
Poor Survival Rates in Leukemia Linked to Persistent Genetic Mutations
For patients with an often-deadly form of leukemia, new research suggests that lingering cancer-related mutations – detected after initial treatment with chemotherapy – are associated with an increased risk of relapse and poor survival.
Searching Big Data Faster
Theoretical analysis could expand applications of accelerated searching in biology, other fields.
Growing Hepatitis C in the Lab
Recent discovery allows study of naturally occurring forms of hepatitis C virus (HCV) in the lab.
Inciting an Immune Attack on Cancer Cells
A new minimally invasive vaccine that combines cancer cells and immune-enhancing factors could be used clinically to launch a destructive attack on tumors.
Reprogramming Cancer Cells
Researchers on Mayo Clinic’s Florida campus have discovered a way to potentially reprogram cancer cells back to normalcy.
Genetic Overlapping in Multiple Autoimmune Diseases May Suggest Common Therapies
CHOP genomics expert leads analysis of genetic architecture, with eye on repurposing existing drugs.
Surprising Mechanism Behind Antibiotic-Resistant Bacteria Uncovered
Now, scientists at TSRI have discovered that the important human pathogen Staphylococcus aureus, develops resistance to this drug by “switching on” a previously uncharacterized set of genes.
How DNA ‘Proofreader’ Proteins Pick and Edit Their Reading Material
Researchers from North Carolina State University and the University of North Carolina at Chapel Hill have discovered how two important proofreader proteins know where to look for errors during DNA replication and how they work together to signal the body’s repair mechanism.
Fat in the Family?
Study could lead to therapeutics that boost metabolism.
Tissue Bank Pays Dividends for Brain Cancer Research
Checking what’s in the bank – the Brisbane Breast Bank, that is – has paid dividends for UQ cancer researchers.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!