Navigation Links
Penn researchers identify new protein important in breast cancer gene's role in DNA repair
Date:3/18/2009

PHILADELPHIA -- For years, researchers have known that under normal conditions, the breast cancer protein BRCA1 orchestrates the repair of damaged DNA, but the details of just how BRCA1 moves to the damaged site and recruits the right nuclear repairmen for DNA restoration remains a mystery.

Now, a new study from the University of Pennsylvania School of Medicine has identified genes associated with the BRCA1 protein and their involvement in the DNA repair pathway, helping to clear the way for researchers to better understand what goes wrong when the BRCA1 gene is mutated and the repair pathway goes haywire. Identifying patients with mutations in these BRCA1-associated genes may help better fight breast cancer.

The new study appears in the most recent issue of Genes & Development.

"A mutated BRCA1 gene increases vulnerability to breast and ovarian cancers by increasing the rate at which genes are altered," says Roger Greenberg, MD, PhD, Assistant Professor of Cancer Biology at the Abramson Family Cancer Research Institute at the University of Pennsylvania. Previous studies have shown that mutated BRCA1-associated proteins also increase the risk of breast cancer, implying that a BRCA1-centered DNA repair pathway is necessary to suppress cancer.

About two years ago, Greenberg helped to lead a study that identified the role of a BRCA1-associated protein called RAP80. The BRCA1 protein works in partnership with RAP80 to locate damaged DNA sites. Cancer-causing mutant BRCA1 proteins fail to pair up with RAP80, which, in turn, blinds BRCA1 to DNA damage. The results of the study led Greenberg's group to look closer at the interaction between BRCA1 and RAP80 to learn the molecular details of how this complex functioned in DNA repair and to explore RAP80 as a possible breast-cancer-susceptibility gene candidate.

In the latest study, Greenberg's team returned to the BRCA1-RAP80 complex for additional analysis, and identified another protein called MERIT40 that works with BRCA1-RAP80 to achieve DNA repair. MERIT40, a previously unknown protein, was revealed by purifying BRCA1-RAP80 complexes from human cells. MERIT40 not only recruits BRCA1 and RAP80 to the sites of DNA damage and signals for DNA repairman to the site, but also acts as the molecular scaffold for the BRCA1-RAP80 complex.

"The BRCA1-RAP80 protein complex works as machine. If a piece of the machine is missing, the machine will begin to break down and eventually stop working," says Greenberg. Without MERIT40, Greenberg's group discovered that the BRCA1-RAP80 complex degrades, denying BRCA1 access to the DNA damage sites within the genome.

The identification of MERIT40 as a BRCA1-associated gene may also lead researchers to other genes that increase vulnerability to breast cancer. Greenberg said the identification of the fundamental role of RAP80 several years ago has led researchers to explore RAP80 as a cancer-causing gene. Greenberg said ongoing studies have confirmed that mutations to the RAP80 gene occur in human populations and may cause cancer. These reports will be published later this year, he said.

"There are many genes associated with BRCA1 that turn out to be mutated in breast cancer," Greenberg said. "MERIT40 now becomes another good gene to study."

Understanding how BRCA responds to damaged DNA can also help scientists to better fight cancer with chemotherapy, notes Greenberg. By shutting MERIT40 genes off, researchers may be able to weaken cancer cells, leaving them more susceptible to attack by chemotherapy.

In the future, Greenberg says he hopes to gain a better understanding of how MERIT40 works by looking for MERIT40 mutations in breast cancer patients.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related medicine news :

1. Fish health claims may cause more environmental harm than good: UBC-St. Michaels researchers
2. Researchers clone key sperm-binding proteins
3. Researchers find sustained improvement in health in Experience Corps tutors over 55
4. Researchers develop DNA patch for canine form of muscular dystrophy
5. University of Pennsylvania researchers find that the unexpected is a key to human learning
6. Researchers discover ways of integrating treatment of traumatized Tibetan refugee monks
7. European Researchers Call for New Doping Standards
8. Researchers Report Combined Molecules in Red Wine by Far Exceed the Biological Activity of Plain Resveratrol, Consistent With the Composition of Longevinex(R)
9. Japanese Researchers Develop New Smallpox Vaccine
10. U of Minnesota researchers examine the value of health information technology
11. A Lesson for Parents: Arguing in Front of Your Teens Has Lasting Impact, Researchers Find
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Penn researchers identify new protein important in breast cancer gene's role in DNA repair
(Date:8/19/2017)... ... , ... “Congratulations! It's A Boy! God’s Gift: A Story of Love”: a ... “Congratulations! It's A Boy! God’s Gift: A Story of Love” is the creation of ... , Published by Christian Faith Publishing, Dale Anthony and Rachael Anthony’s new book is ...
(Date:8/18/2017)... VA (PRWEB) , ... August 18, 2017 , ... More ... the Democratic Republic of Congo (DRC) thanks to an ambitious venture that conjoined the ... well as the generous support of the Liberty community. These shoes will save lives ...
(Date:8/18/2017)... , ... August 18, 2017 ... ... Quick International, LLC (“Quick”), a highly specialized asset-light logistics provider of complex ... into a definitive agreement to purchase Unitrans International Corporation, a division of ...
(Date:8/18/2017)... (PRWEB) , ... August 18, 2017 , ... ... this summer’s edition of “Vision & Hearing,” advocating for active, healthy lifestyles and ... on resources available for individuals with hearing impairments and shares the latest innovations ...
(Date:8/18/2017)... (PRWEB) , ... August 18, 2017 , ... ... liquid handling handheld devices. Through an educational webinar, they will present the line ... a chance to learn how easy you can automate everyday pipetting tasks. , ...
Breaking Medicine News(10 mins):
(Date:8/7/2017)... Aug. 7, 2017  Endo International plc (NASDAQ: ... to resolve virtually all known U.S. mesh product liability ... resolve the known remaining U.S. claims at reasonable values. ... in the fourth quarter of 2017 and continuing through ... second quarter 2017 results, the Company intends to increase ...
(Date:8/3/2017)... SAN DIEGO , Aug. 3, 2017  Opioid ... crippling diseases driving up healthcare costs and threatening outcomes, ... the lab supply and IVD industry that support them, ... health care market researcher said that drugs of abuse, ... vendors and sessions at the organization,s 69th meeting in ...
(Date:8/2/2017)... Flight Network and PeaceHealth Oregon Network announced they renewed a ... efficiency for patients at hospitals in Eugene ... , and Florence, Oregon , who ... work collaboratively to move patients who require the highest level ... emergency exists. PeaceHealth ...
Breaking Medicine Technology: