Featured Research

from universities, journals, and other organizations

SUMO works with replication protein A complex to repair DNA

Date:
August 15, 2010
Source:
University of Texas M. D. Anderson Cancer Center
Summary:
Researchers have shown for the first time that the small protein SUMO can team up with the replication protein A complex to facilitate DNA repair.

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.

Related Articles


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."

]

Funding for this research was provided by the National Institutes of Health.

Co-authors with Yeh are first author Hong Dou, Ph.D., also of MD Anderson's Department of Cardiology; Chao Huang, Ph.D. of the Texas Heart Institute/St. Luke's Episcopal Hospital; Melissa Singh, Ph.D. of MD Anderson's Children's Cancer Hospital and the University of Texas Health Science Center at Houston; and Phillip B. Carpenter, Ph.D. of the University of Texas Health Science Center at Houston.


Story Source:

The above story is based on materials provided by University of Texas M. D. Anderson Cancer Center. Note: Materials may be edited for content and length.


Cite This Page:

University of Texas M. D. Anderson Cancer Center. "SUMO works with replication protein A complex to repair DNA." ScienceDaily. ScienceDaily, 15 August 2010. <www.sciencedaily.com/releases/2010/08/100812122611.htm>.
University of Texas M. D. Anderson Cancer Center. (2010, August 15). SUMO works with replication protein A complex to repair DNA. ScienceDaily. Retrieved March 5, 2015 from www.sciencedaily.com/releases/2010/08/100812122611.htm
University of Texas M. D. Anderson Cancer Center. "SUMO works with replication protein A complex to repair DNA." ScienceDaily. www.sciencedaily.com/releases/2010/08/100812122611.htm (accessed March 5, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, March 5, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Bupa Eyes India Healthcare Opportunities

Bupa Eyes India Healthcare Opportunities

Reuters - Business Video Online (Mar. 5, 2015) Bupa is hoping to expand in India&apos;s fast-growing health insurance market, once a rule change on foreign investment is implemented. The British private healthcare group&apos;s CEO tells Grace Pascoe why it&apos;s so keen on the new opportunity. Video provided by Reuters
Powered by NewsLook.com
Doctor in Your Pocket Is Getting Smarter

Doctor in Your Pocket Is Getting Smarter

Reuters - Business Video Online (Mar. 5, 2015) Mobile apps are turning smartphones into a personal doctors, with users able to measure heart rate, blood pressure and even blood sugar. But will it change our behaviour? Ivor Bennett reports from the Mobile World Congress in Barcelona. Video provided by Reuters
Powered by NewsLook.com
AbbVie Inks $21B Deal To Buy Cancer Drugmaker Pharmacyclics

AbbVie Inks $21B Deal To Buy Cancer Drugmaker Pharmacyclics

Newsy (Mar. 5, 2015) AbbVie announced Wednesday it will buy cancer drugmaker Pharmacyclics in a $21 billion deal. Video provided by Newsy
Powered by NewsLook.com
Toddlers Drinking Coffee? Why You Shouldn't Share Your Joe

Toddlers Drinking Coffee? Why You Shouldn't Share Your Joe

Newsy (Mar. 5, 2015) A survey of Boston mothers and toddlers found that 15 percent of two-year-olds drink coffee and 2.5 percent of 1-year-olds. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins