Drexel University and Georgia Institute of Technology researchers have discovered how the Rad52 protein is a crucial player in RNA-dependent DNA repair. The results of their study, published June 8 in the journal Molecular Cell, uncover a surprising function of the homologous recombination protein Rad52. They also may help to identify new therapeutic targets for cancer treatment.
Radiation and chemotherapy can cause a DNA double-strand break, one of the most harmful types of DNA damage. The process of homologous recombination — which involves the exchange of genetic information between two DNA molecules — plays an important role in DNA repair, but certain gene mutations can destabilize a genome. For example, mutations in the tumor suppressor BRCA2, which is involved in DNA repair by homologous recombination, can cause the deadliest form of breast and ovarian cancer.
Alexander Mazin, a professor at Drexel University’s College of Medicine, and Francesca Storici, an associate professor at Georgia Tech’s School of Biological Sciences, have dedicated their research to studying mechanisms and proteins that promote DNA repair.
In 2014, Storici and Mazin made a major breakthrough when they discovered that RNA can serve as a template for the repair of a DNA double-strand break in budding yeast, and Rad52, a member of the homologous recombination pathway, is an important player in that process.
“We provided evidence that RNA can be used as a donor template to repair DNA and that the protein Rad52 is involved in the process,” said Mazin. “But we did not know exactly how the protein is involved.”
In their current study, the research team uncovered the unusual, important role of Rad52: It promotes “inverse strand exchange” between double-stranded DNA and RNA, meaning that the protein has a novel ability to bring together homologous DNA and RNA molecules. In this RNA-DNA hybrid, RNA can then be used as a template for accurate DNA repair.
It appeared that this ability of Rad52 is unique in eukaryotes, as otherwise similar proteins do not possess it.
“Strikingly, such inverse strand exchange activity of Rad52 with RNA does not require extensive processing of the broken DNA ends, suggesting that RNA-templated repair could be a relatively fast mechanism to seal breaks in DNA,” Storici said.
As a next step, the researchers hope to explore the role of Rad52 in human cells.
“DNA breaks play a role in many degenerative diseases of humans, including cancer,” Storici added. “We need to understand how cells keep their genomes stable. These findings help bring us closer to a detailed understanding of the complex DNA repair mechanisms.”
The research was supported by the National Institutes of Health, the National Science Foundation and the Howard Hughes Medical Institute.
These results offer a new perspective on the multifaceted relationship between RNA, DNA and genome stability. They also may help to identify new therapeutic targets for cancer treatment. It is known that active Rad52 is required for proliferation of BRCA-deficient breast cancer cells. Targeting this protein with small molecule inhibitors is a promising anticancer strategy. However, the critical activity of Rad52 required for cancer proliferation is currently unknown.
This new Rad52 activity in DNA repair, discovered by Mazin, Storici and their team, may represent this critical protein activity that can be targeted with inhibitors to develop more specific — and less toxic — anti-cancer drugs. Understanding of the mechanisms of RNA-directed DNA repair may also lead to development of new RNA-based mechanisms of genome engineering.
This research was supported by the National Institute of General Medical Sciences (NIGMS) of the NIH (grant GM115927), the National Science Foundation (grant 1615335), and the Howard Hughes Medical Institute Faculty Scholar Program (grant 55108574). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the sponsoring agencies.
Written by Drexel University.
CITATION: Olga M. Mazina, Havva Keskin, Kritika Hanamshet, Francesca Storici,
Alexander V. Mazin, “Rad52 Inverse Strand Exchange Drives RNA Templated
DNA Double-Strand Break Repair,” (Molecular Cell, 2017). http://dx.doi.org/10.1016/j.molcel.2017.05.019
Research News
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Join us for the official launch of the Drawdown Georgia Business Compact!
What do Anthem, Cox Enterprises, Delta Air Lines, Google, and UPS have in common? They are all founding members of the Drawdown Georgia Business Compact—a unique state-centered collaborative initiative focused on galvanizing climate action in Georgia.
The Ray C. Anderson Center for Sustainable Business invites you to participate in the official launch of the Compact on Thursday, October 21 from 2:00 to 3:00 p.m. The virtual launch event will feature a panel of founding members moderated by Maryam Alavi, Dean of the Georgia Tech Scheller College of Business.
The Compact’s mission is to leverage the collective impact of our state’s business community to achieve net zero carbon emissions in Georgia by 2050 through a just, competitive, and sustainable transition.
Founding compact members: Anthem, Better Earth, Cox Enterprises, Delta Air Lines, Eversheds Sutherland, Goodr, Google, Interface, Norfolk Southern, Southwire, TKE, UPS, and YKK.
Moderator:
Maryam Alavi, Dean, Georgia Tech Scheller College of Business
Panelists:
Jasmine Crowe, Founder and CEO, Goodr
Savannah Miller, Vice President of Sustainability, Better Earth
Nick Pearson, Global Head of Energy Policy, Google
Josh Raglin, Chief Sustainability Officer, Norfolk Southern
We encourage you to join us for future Compact events. Subscribe to email updates from the Ray C. Anderson Center for Sustainable Business.
For more information on how to join the Drawdown Georgia Business Compact, visit the Drawdown Georgia Business Compact website or contact David Eady by email (david.eady@gatech.edu) or phone (404-894-3038).
About the Ray C. Anderson Center for Sustainable Business:
The Ray C. Anderson Center for Sustainable Business was founded in 2013 to act as a catalyst and connector, bringing together students, research faculty, companies, and entrepreneurs to create an environment where business-driven solutions to sustainability challenges can take shape and thrive. In all, Scheller provides students unparalleled breadth in environmental sustainability, ethics, corporate social responsibility, social entrepreneurship, and values-based leadership.
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Stop by for free drop-in math help today! The Outdoor Math Lab is open M-Th 11-6pm and Fri 11-3pm in the Skiles Courtyard. It is staffed by School of Math Teaching Assistants in coordination with Tutoring & Academic Support.
https://tutoring.gatech.edu/drop-in/
The Math Lab will be closed during school breaks.
Event Details
Stop by for free drop-in math help today! The Outdoor Math Lab is open M-Th 11-6pm and Fri 11-3pm in the Skiles Courtyard. It is staffed by School of Math Teaching Assistants in coordination with Tutoring & Academic Support.
https://tutoring.gatech.edu/drop-in/
The Math Lab will be closed during school breaks.
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Speakers:
Kevin Nepveux, M.S.
VP, Launch Excellence
Pfizer
Kevin Nepveux is Vice President, Launch Excellence. Kevin’s responsibilities include the creation of new technology and manufacturing modalities to support the co-development and launch processes. This function leads PGS Co-Development Teams and provides a single point of accountability for new product activities within PGS and to our internal stakeholders (WRD, Commercial Business Units). He joined Pfizer in 1980 at Groton, Connecticut, as a Production Supervisor in the penicillin area. In 1985, he moved to R&D to work on azithromycin, danofloxacin and other projects. Kevin managed the Groton Active Pharmaceutical Ingredient pilot plant until 1995, when he returned to manufacturing in a technical services position. As manufacturing grew and became more specialized, he focused on technical and project management support for new products as part of Global Manufacturing Services (GMS). For several years, he led a group within GMS working with Pfizer Global R&D and the PGS launch sites to develop and introduce new products. In his current position, Kevin leads the Global Technology Services organization in providing technical leadership and support for new and marketed products for all PGS customers.
Previous to his current role Kevin was Vice President, Global Technology Services. Kevin holds a B.S. in Chemical Engineering from the University of Delaware and an M.S. in Computer Science from Rensselaer Polytechnic Institute
James Jean, M.B.A.
Director, Temperature Control Logistics,
Pfizer Global Supply
James Jean is the Director of Temperature Control Logistics for Pfizer Global Supply Chain. James leads a global team of engineers and technical subject matter experts responsible for Pfizer Global Supply Chain's temperature sensitive product portfolio. Most recently, James has successfully led his team in developing supply chain capabilities for the launch of the Pfizer COVID-19 Vaccine across many global markets.
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Questions are being collected in advance for our Georgia Tech, October 21, Pfizer lecture with Kevin Nepveux and James Jean.
Submit your question(s) HERE.
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This talk: The global lockdown to mitigate COVID-19 health risks both reduced human interactions with nature, while increasing interactions with animals indoors. We've documented the impacts of temporary human absence from nature on wild and domestic animal behaviors- some good, and some bad. Come hear about (and see in action!) how our furry, feathered, and scaly friends have responded to lockdown along with us.
Emily Weigel, Ph.D. (she/her) is currently a Senior Academic Professional in the School of Biological Sciences at the Georgia Institute of Technology, in Atlanta, Georgia. Originally from Atlanta, Weigel earned dual doctorates from Michigan State University in Zoology and in Ecology, Evolutionary Biology, and Behavior. Now at Georgia Tech, she has received an incredible number of awards, many from student nominations that have recognized her passion and drive for their success. Dr. Weigel has helped develop several classes at Georgia Tech, including on Climate Change in Urban Spaces and Stream Ecology, and regularly studies factors governing student success. Her work in biology education, ecology, and conservation is regularly published in academic journals, and she is frequently a referenced source in academia, especially to help popular science audiences understand biology.
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Michael Goodisman, Ph.D.
School of Biological Sciences
Georgia Institute of Technology
Attend BlueJeans Event
The evolution of sociality represented one of the major transition points in biological history. I am interested in understanding how evolutionary processes affect social systems and how sociality, in turn, affects the course of evolution. My research focuses on the molecular basis underlying sociality, the nature of selection in social systems, the breeding biology of social animals, the process of self-organization in social groups, and the course of development in social species.
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In February 2021, NASA's Perseverance rover landed successfully at the Octavia E. Butler Landing Site in the Jezero Crater, the site of an ancient open-system lake on Mars. Perseverance is seeking signs of ancient life, and is collecting Martian rock and soil samples for possible return to Earth by a future mission. Upon completing a 90-day commissioning phase, Perseverance embarked on an exploration and sampling campaign of the rocks and outcrops comprising the present-day floor of Jezero Crater. This abstract summarizes the mission results from Perseverance's first eight months on Mars, including the lead-up to the collection of the mission's first sample.
Virtual talk: 11:25 a.m.-12:15 p.m. via Blue Jeans: http://primetime.bluejeans.com/a2m/live-event/udqsqwfd
Social Event: 4-6 p.m., Molecular Science and Engineering Building, ground floor outdoor patio
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In this fifth townhall of the Georgia Tech Covid-19 Surveillance Testing series, Greg Gibson and Joshua S. Weitz, Patton Distinguished Chairs and professors in Biological Sciences, will be joined by Nga Lee (Sally) Ng, professor in Chemical & Biomolecular Engineering and in Earth and Atmospheric Sciences, to provide updates and insights related to the new school year and fall semester. Participants will have an opportunity to pose questions during this virtual event. This townhall will be recorded, and a recap will be posted here following the event.
Join the event on BlueJeans by tapping this link.
Watch previous townhalls in this series:
- Covid-19 Testing, Vaccination, and Mitigation Townhall
(May 5, 2021) - Covid-19 Cases Rise, Holiday Travel and Stopping the Spread (November 16, 2020)
- Campus Surveillance Testing Update: Tracking Cases and Taking Action (September 10, 2020)
- Georgia Tech Surveillance Testing: Update and Early Interpretations (August 20, 2020)
Watch previous related talks:
- Covid-19 Response Efforts: Chemistry and Biochemistry at Georgia Tech (April 16, 2020)
- Dynamics of COVID-19: Near- and Long-term Challenges with Joshua S. Weitz (April 15, 2020)
- Georgia Tech CMDI Science Forum Spotlights Coronavirus Outbreak (February 10, 2020)
This series is hosted by the School of Biological Sciences at Georgia Tech.
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