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

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