Navigation Links
Protein's essential role in repairing damaged cells revealed
Date:1/6/2009

ANN ARBOR, Mich. University of Michigan researchers have discovered that a key protein in cells plays a critical role in not one, but two processes affecting the development of cancer.

"Most proteins involved in responding to DNA damage that can cause cancer either help detect the damage and warn the rest of the cell, or help repair the damage," says David O. Ferguson, M.D., Ph.D., the study's lead author. Ferguson is an assistant professor of pathology at the U-M Medical School and a member of U-M's Comprehensive Cancer Center.

Prior research has shown that the protein, Mre11, functioned as a "gatekeeper" to signal injury to the cell and prevent damaged cells from proliferating. Now, Ferguson and colleagues have discovered that in mammals, a function of the Mre11 protein also serves as a "caretaker," by repairing DNA.

Their findings, published in the journal Cell, could have important implications for cancer treatment by someday allowing oncologists to predict a tumor's sensitivity to radiation and other therapies, making it more vulnerable to treatment.

Under normal circumstances, the body's cells grow, divide and eventually die. When something damages a healthy cell's DNA -- such as radiation or exposure to a toxin -- a multiprotein complex steps in to repair the breakage and activate other fundamental cellular processes.

The MRN complex, comprised of the Mre11, Rad50 and NBS1 proteins, senses DNA damage, known as double-strand breaks, within the cell. The complex then transmits that information to an enzyme called the ATM (ataxia-telangiectasia mutated) checkpoint kinase.

The ATM kinase controls the cell's response to double-strand breaks, and slows cell growth to give the cell opportunities to repair them, says Ferguson.

When the MRN complex doesn't work properly, inherited human neurological diseases, such as ataxia-telangiectasia-like syndrome and Nijmegen breakage syndrome, result. Both feature MRN mutations and significantly predispose a person to immunodeficiency and cancer.

What Ferguson and colleagues discovered is that Mre11 not only senses and communicates damage, it also repairs DNA double-strand breaks by acting as a nuclease, an enzyme that modifies and processes the broken DNA ends.

Research details

The researchers generated mouse models to examine the exact role of Mre11 in the MRN complex. They engineered two mouse strains, one in which Mre11 was disabled completely, and one in which only a single amino acid change was made.

What surprised researchers the most was that making that change to a single amino acid in Mre11 caused consequences as severe as when they eliminated the entire MRN complex.

Taking out the amino acid in Mre11 responsible for nuclease activity caused the mice to develop growth defects, chromosomal abnormalities and sensitivity to DNA-damaging agents. Therefore, researchers could say that the nuclease, or repair, activity of Mre11 proves critical for both MRN function and stability of the genetic material of the organism.

"First, Mre11 signals to the cell by activating the kinase, but it also acts in the repair of double-strand breaks via the nuclease functions. Therefore, it prevents the two individual steps that lead to cancer," Ferguson says.

Implications

The work, called "virtuoso cell engineering" in a Cell preview article, holds particular promise for identifying mutations associated with many cancers.

"What's emerging in the literature from large-scale screening studies of human tumors is that Mre11 may be frequently mutated in certain cancers," Ferguson says.

"This may have implications for diagnoses because tumors associated with different mutations may have different prognoses and respond to different therapies," he says. In particular, mutations in Mre11 may predict how sensitive or resistant a particular tumor will be to treatments with DNA-damaging agents.

"The fact that we have now separated the functions of DNA repair from the checkpoint functions means we may have identified a target that can sensitize tumors to radiation and chemotherapeutic agents used in treating cancer."


'/>"/>

Contact: Nicole Fawcett
nfawcett@umich.edu
734-764-2220
University of Michigan Health System
Source:Eurekalert  

Related medicine news :

1. 2 Cardiovascular Proteins Tied to Severity of Alzheimers
2. Two cardiovascular proteins pose a double whammy in Alzheimers
3. Stopping ovarian cancer by blocking proteins coded by notorious gene
4. Mutant proteins result in infectious prion disease in mice
5. Quintet of proteins forms new, early-warning blood test before heart attack strikes
6. Elaborate Network Drives When and Where Proteins Are Made
7. DIA/AAPS Co-Sponsored Conference to Examine the Immunogenicity of Therapeutic Proteins
8. Pressured proteins: A little pressure in proteomics squeezes 4-hour step into a minute
9. Discovery of key malaria proteins could mean sticky end for parasite
10. Zinc finger proteins put personalized HIV therapy within reach
11. DSM and Crucell Sign Agreement with Avid Bioservices to Serve as First Pre-Approved U.S. Contract Manufacturer of PER.C6(R) Cell Line Proteins
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Protein's essential role in repairing damaged cells revealed
(Date:4/30/2016)... ... 30, 2016 , ... “Aging well is a challenge for all of us, but there are things we can ... Kohli . “Research is showing more and more that there are simple, yet important steps ... as we age.” Top priorities Dr. Kohli’s recommends for her patients include;, , ...
(Date:4/29/2016)... ... 29, 2016 , ... Since launching its annual volunteer campaign ... the footwear industry, has broken all previous participation records in its first two ... states during the months of April and May, the 2016 Footwear Cares initiative ...
(Date:4/29/2016)... ... April 29, 2016 , ... ... our nation’s productivity, stability, even security. Most importantly, employees are the single most ... why are American workers so unhappy? , Just under half of American workers ...
(Date:4/29/2016)... , ... April 29, 2016 , ... ... reveals that infants born with severe congenital diaphragmatic hernia have better survival rates ... with congenital diaphragmatic hernia (CDH)—a condition where the diaphragm fails to form completely, ...
(Date:4/29/2016)... ... April 29, 2016 , ... The Gluten-Free ... is pleased to announce the launch of the GFCP Scoop in ... more. The purpose of the GFCP Scoop site is to keep ...
Breaking Medicine News(10 mins):
(Date:4/27/2016)... , April 27, 2016  Bayer Animal Health ... senior from the University of Florida College of ... Bayer Excellence in Communication Award (BECA). Brittany was ... were awarded a total of $70,000 in scholarship ... four years, Bayer has provided a total of ...
(Date:4/27/2016)... 27, 2016 Global  urinalysis ... billion by 2022, according to a new report ... (Logo: http://photos.prnewswire.com/prnh/20150105/723757 ) , ... efficiency and accuracy delivered by the new generation ... novel urinalysis instruments and consumables. For instance, the ...
(Date:4/26/2016)... Hill-Rom Holdings, Inc. (NYSE: HRC ) ... Deutsche Bank 41 st Annual Health Care Conference on ... You are invited to listen to the live discussion via ... directly at http://edge.media-server.com/m/p/mr4uxgas . A recorded replay of the ... live event and accessible at the links above until August ...
Breaking Medicine Technology: