Navigation Links
SUMO works with replication protein A complex to repair DNA
Date:8/12/2010

HOUSTON - A team of investigators led by a physician-scientist at The University of Texas MD Anderson Cancer Center has shown for the first time that the small protein SUMO can team up with the replication protein A (RPA) complex to facilitate DNA repair. The study is published in the Aug. 13 edition of the journal Molecular Cell.

RPA 70 is a component of multiprotein machinery called the RPA complex, which plays a crucial role in DNA replication and repair. The researchers discovered that RPA70 is associated with a SUMO-specific protease called SENP6 during a part of the cell cycle in which DNA replication occurs. They also discovered that RPA70 can be modified by SUMO, and this modification is regulated by SENP6.

"In this paper, we show the modification of RPA70 by SUMO is essential to repair DNA double-string breaks by homologous recombination," said corresponding author Edward T.H. Yeh, M.D., professor and chair of MD Anderson's Department of Cardiology. "If a mutant protein that cannot be modified by SUMO is substituted for RPA70, the cells are much more sensitive to chemotherapy and ionized radiation."

The chemotherapy drug camptothecin and ionizing radiation both attack cancer cells by causing double-strand DNA breaks. Cells respond by activating homologous recombination to repair the damage. The newly discovered connection between SUMO and RPA70 offers a potential target for short-circuiting repair, making the cells more vulnerable to treatment.

Team Has Made Multiple Discoveries

This research is one more piece in a multi-faceted puzzle Yeh and his colleagues have been working on since 1996. Yeh discovered a post-translational protein modification system that rivals ubiquitination in complexity and importance:

  • SUMO (small ubiquitin-related modifier) proteins, originally called Sentrin, which attach to other proteins and modify their function or physically move them within the cell (SUMOylation)

  • Sentrin/SUMO-specific protease (SENP), which removes SUMO from proteins (de-SUMOylation)

Mammalian cells have six SENPs, and Yeh's group is looking systematically at all of them. Their previous research has shown SENP1 enables cells to survive at low oxygen levels, which is key for development of many kinds of cancer. And, earlier this year, they reported that SENP2 plays an important part in embryonic development.

SENP6 Regulates Several Proteins

To investigate SENP6, the researchers knocked down the messenger RNA that encodes SENP6 in cultured cells. They found that SENP6 plays a key role in progression of the cell cycle, and that it regulates a number of proteins, including RPA70. SENP6 associates with RPA70 in the S-phase of the cell cycle, when DNA is replicated, preventing SUMOylation of RPA70.

"We found that when SENP6 is removed from RPA70, RPA70 has the potential to be modified by a specific type of SUMO called SUMO2/3," Yeh said. "So we asked the question, 'Can we actually cause premature or artificial separation of SENP6 and RPA70?

"This led to the discovery that the chemotherapy drug camptothecin dissociates SENP6 from RPA70, allowing it to be modified by SUMO 2/3. In addition, we found these proteins can be separated by ionized radiation," Yeh said.

SUMO 2/3 Necessary to Repair Cell Damage

RPA70 that has been modified by SUMO 2/3 recruits RAD51, an important protein in the repair of DNA damage through homologous recombination. When a mutant that cannot be SUMOylated is substituted for RPA70, the repair process is defective, giving the cell increased sensitivity to camptothecin and radiation.

"To repair DNA double-string breaks and damages, you need SUMO 2/3 to be there for the repair to occur efficiently," Yeh said. "RPA70 is a crucial protein in both DNA replication and repair, and we've demonstrated its relationship to DNA repair and why SUMOylation is important to this process."


'/>"/>

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

Related medicine news :

1. KPA and TK Carsites offer HR, OSHA and Internet Marketing Workshops at the NADA Convention and Expo 2010
2. For Some Breast Cancer Patients, Shorter Radiation Works Well
3. Swine Flu vaccination: voluntary system works
4. mHealth Alliance Works in Partnership with GSMA to Expand Discussion of Mobile Health at 2010 Mobile World Congress
5. BCS Global Launches PSVN (Public Switched Video Network), an Initiative to Provide a Framework for Inter-Connecting Business to Business Video Networks
6. Visionworks(R) Brings High Quality Eye Care & Eye Wear to Western PA
7. Dr. Alesia Wagner of U.S. HealthWorks Medical Group Re-elected to Board of Osteopathic Physicians and Surgeons of California
8. Abbott Research Group, Inc. Launches New Product - WaterWorks
9. Learn to Dance in a Day -- Beginner Workshop Launches Modern Jive in Toronto
10. Enterprise PDM Integration has Never Been Easier; Zero Wait-State Announces Leading SolidWorks Reseller GoEngineer as Master Distributor for DesignState
11. Easy to See and Use Senior Phone Works with AT&T and T-Mobile Cellular Providers
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
SUMO works with replication protein A complex to repair DNA
(Date:5/27/2016)... , ... May 27, 2016 , ... This campaign aims ... stroke, which we as a society can control and change. , As nearly 795,000 ... every 40 seconds within the United States. Plus, with an estimated 129,000 of these ...
(Date:5/27/2016)... ... May 27, 2016 , ... Aimed at nurses ... human interest stories, courtesy of leaders in the nursing and health care industry. ... from leading advocates and associations—namely Jones & Bartlett Learning. , Jones & Bartlett ...
(Date:5/26/2016)... ... ... last week’s media reports hinting at a June rate hike after the Federal Reserve’s ... interest rate increase, according to Rajeev Dhawan of the Economic Forecasting Center at Georgia ... (FOMC) dot charts are of interest to the press for their noise potential,” Dhawan ...
(Date:5/26/2016)... ... May 26, 2016 , ... Intalere, the healthcare industry ... for its inaugural Member Conference at the Paris Hotel in Las Vegas, Nev., ... health of America’s healthcare providers. , The conference was highlighted by the announcement ...
(Date:5/26/2016)... ... , ... The Woodlands at John Knox Village , Florida’s first Life ... living and healing, celebrated its grand opening, today. The Woodlands at John Knox Village ... Empowered Staff. , “This is an incredibly fulfilling time for John Knox Village as ...
Breaking Medicine News(10 mins):
(Date:5/25/2016)... Texas , May 25, 2016 ... the issuance to it by the US Patent ... The company,s technology includes proprietary processes for electronic ... for health and wellness programs, HIPAA compliance and ... "Our technology ...
(Date:5/24/2016)... AMSTERDAM , May 24, 2016 ... aplicación médica para ayudar a los médicos a compartir ... los pacientes a escala mundial. Profesionales médicos de Europa, ... ya se han apuntado a la aplicación, que combina ... en un entorno totalmente seguro. Educación   ...
(Date:5/24/2016)... LAWRENCE, Mass. , May 24, 2016  NxStage ... medical technology company focused on advancing renal care, today ... Officer, plans to participate in the following schedule of ... will be made available at http://ir.nxstage.com/ . ... Jefferies Healthcare Conference NY, NY           Friday, ...
Breaking Medicine Technology: