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:2/23/2017)... , ... February 23, 2017 , ... CALNOC, the nation’s ... FACPE, will keynote their upcoming conference – Empowerment, Value and Collaboration – in Seattle, ... and CEO of the Virginia Mason Health System in Seattle since 2000. In addition ...
(Date:2/23/2017)... , ... February 23, 2017 , ... Thomas Vas-Don ... and disciplined exercise regime, the author was able to successfully recover. In “ Origin ... relevant information for various sources on the principals of massage, anatomy , ...
(Date:2/22/2017)... Raton, FL (PRWEB) , ... February 22, 2017 , ... ... primarily from deer antler velvet, announced its products are coming soon to Amazon.com, the ... Clint and Shelley Thomson as a means to develop an effective natural treatment for ...
(Date:2/22/2017)... ... February 22, 2017 , ... The National Academy of Certified ... the April 2017 testing period. NACCM, a nonprofit organization, has provided the premier ... exam is periodically re-calibrated to ensure that newly certified professionals are prepared to ...
(Date:2/22/2017)... Burlingame, CA (PRWEB) , ... February 22, 2017 ... ... of American adults with chronic conditions reported skipping doses or not filling a ... were uninsured or under-insured, rates of cost-related problems getting medications were 30-60%*. ...
Breaking Medicine News(10 mins):
(Date:2/23/2017)... 2017  As National Nutrition Month approaches, USA Medical ... is helping people live healthier lives by providing ... programs in all 50 states including:  Texas Prescription ... California Prescription Assistance Program . USA Medical ... for nutritious eating habits: ...
(Date:2/23/2017)... LG Innotek today announced that the company has developed the world,s ... is 1.5 times higher than the competitor,s 45mW module. ... of 200 -- 280nm, allowing it to be used for sterilization purpose. ... Innotek,s product emits UV in the range of 280nm. ... Until now, UV-C LED has ...
(Date:2/23/2017)... February 23, 2017 Tillotts Pharma ... Berlin office was opened in ... . The portfolio includes Entocort ® for the ... treatment of ulcerative colitis, and VistaPrep ® for ... Swiss specialty pharmaceutical company focused on the treatment of ...
Breaking Medicine Technology: