Navigation Links
Replication at DNA damage sites highlights Fanconi anemia and breast cancer proteins
Date:9/10/2009

HOUSTON - While Fanconi anemia (FA) is a rare and dangerous disease, new laboratory research at The University of Texas M. D. Anderson Cancer Center shows it may lead researchers toward clues in more common diseases, including highly hereditary types of breast cancer.

In a study published in the Sept. 11 issue of the journal Molecular Cell, scientists report that recruitment of proteins to DNA damage sites is controlled by replication in both FA and BRCA cancer proteins.

Lei Li, Ph.D, professor in Experimental Radiation Oncology at M. D. Anderson, and corresponding author of the study, has spent much of his 15-year career studying how the body repairs DNA damage. He says DNA crosslinks are the most severe type of DNA damage; they're actually turned against cancer in certain drugs, including cisplatin.

Answers have been elusive

People with FA, a hereditary disease, are extremely sensitive to DNA crosslinks and at a very high risk for cancer. How the Fanconi pathway protects cells from DNA crosslinks and whether FA proteins act directly on crosslinks has remained unclear despite extensive research.

"Our lab has been working for almost 10 years on why FA cells are so sensitive to crosslinking," Li said. "We've known it must have something to do with how they deal with DNA crosslinks, but this is the first time we've been able to pinpoint a reason for some of them."

FA involves 13 genes; a mutation in any one of them can cause the disease. Three of the FA genes recently were found to be identical to breast cancer susceptibility genes BRCA2, BACH1 and PALB2.

"This led us to begin to examine breast cancer genes, since we thought they might have something to do with the repair of DNA crosslinkers," Li said.

Researchers developed a novel genetic technique, eChIP, a chromatin-IP-based strategy, to examine FA proteins with DNA crosslinks.

"The model scientists have been following for many years is that all 13 genes must work together to deal with DNA crosslinks, that there must be some kind of cascade or chain reaction," Li said. "We developed a new genetic technique to look specifically at what proteins are present at the crosslinks."

New method yields answers

Using this new tool, researchers found that all the FA genes are present in the site of a crosslink. This is the first time FA proteins have been linked directly with DNA crosslinking damage at the molecular level.

"The surprise is that the breast cancer proteins, although they are present at crosslinks, must have DNA replication at the crosslinks," Li said. "If there is a DNA lesion on the genome but no DNA replication, the canonical FA proteins are used to deal with the damage. The breast cancer-related FA proteins are taking care of the DNA lesion that stops DNA replication."

Li said this leads to a new paradigm that there must be two separate subgroups or subpathways within the 13 FA genes.

"The major implication of this study is that now we have a new working model," Li said. "This provides a new direction for future research of breast cancer proteins and DNA damage response in general.

"Our next step is to continue to look at how FA proteins and the subgroup of breast cancer-related proteins help protect cells from DNA crosslink damage. And, in a more general sense, how these cellular mechanisms eventually may help us minimize mutations that ultimately lead to cancer."


'/>"/>

Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

Related medicine news :

1. Childrens Hospital Boston Deploys AutoVirt Solution to Increase Speed and Efficiency of Windows Data Replication
2. Compounds that trigger beta cell replication identified by JDRF funded researchers
3. Burnham researchers illuminate mechanisms that regulate DNA damage control and replication
4. Herpes drug inhibits HIV replication, but with a price
5. New Compound Slows HIV Replication
6. New agent strikes at respiratory syncytial virus replication
7. Health and Pension Benefits Provider Turns to Xiotechs TimeScale Replication Services to Protect Critical Data
8. FDA Investigating Weight-Loss Drug Over Reports of Liver Damage
9. Pot Might Blunt Damage of Binge Drinking
10. Blood test can detect brain damage in amateur boxers
11. DEET in Bug Spray Tied to Neural Damage in Mice
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:8/18/2017)... ... August 18, 2017 , ... ... services to communities in east Texas, is launching a regional charity effort to ... Founded in 1991, the Pediatric Brain Tumor Foundation (PBTF) has raised nearly $30 ...
(Date:8/18/2017)... Bedford, TX (PRWEB) , ... August 18, 2017 , ... ... serves communities in the Dallas/Fort Worth area, is spearheading a regional charity campaign organized ... her husband. , In early June of this year, Christina and her children returned ...
(Date:8/18/2017)... ... 2017 , ... Alcovit, a lime-flavored beverage that rids the body of toxins ... product now available through Jet.com. , After 25 years of development, the company ... designed to quickly detox the body thereby avoiding alcohol-induced hangovers. Whether you’re having fun ...
(Date:8/18/2017)... , ... August 18, 2017 , ... “Dangerous Inheritance”: a ... author, Diane Winters. Diane is from Southwest Nebraska where she was raised on ... and family. The story is fictional, but the friendships and mantra of ‘neighbors ...
(Date:8/18/2017)... ... August 18, 2017 , ... Rollon Skin ... anti-aging skincare solutions, recently announced the launch of two new skincare products, ... yet effective alternative to expensive plastic surgery or in-patient cosmetic dermatological procedures. , ...
Breaking Medicine News(10 mins):
(Date:8/4/2017)... -- Agragen, LLC, a Cincinnati -based ... and aquacultural feed sectors, announces a significant step ... AGR131.  This drug is designed to trap and ... patients suffering from inflammatory conditions such as rheumatoid ... Biological pharmaceuticals currently used ...
(Date:8/2/2017)...   Marshall County Hospital in Benton, Kentucky has added ... hospital-acquired infections (HAIs). The new addition, Tru-D SmartUVC , short for "total room ultraviolet ... such as C. diff , MRSA, MERS, Ebola and more. ... Tru-D SmartUVC ... Tru-D in action in a patient room ...
(Date:8/1/2017)...   CerSci Therapeutics , a non-opioid drug development ... has received notice from the National Institute on Drug ... that it has been awarded a Direct-to-Phase II Small ... 2017 with an additional $1,000,000 to follow in 2018. ... of their lead non-opioid drug candidate CT-044 to the ...
Breaking Medicine Technology: