Published in today’s issue of Molecular Cell, their paper entitled “A RAP1/TRF2 Complex Inhibits Non-Homologous End Joining at Human Telomeric DNA Ends” employed a biochemical assay for double-strand break repair to define the minimal requirements for the protection of telomeric DNA at the ends of chromosomes.
“Surprisingly, we found that neither long single-stranded overhangs nor t-loop formation is essential to prevent illegitimate repair of telomeric ends,” said Dr. Bae. “Instead, a short tandem array of telomeric repeats bound by a Rap1/Trf2 complex is sufficient to impede non-homologous end joining in a highly directional manner.”
It has long been understood that chromosome ends are distinct from DNA double-strand breaks and that the cellular machinery that repairs DNA breaks does not act on telomeres. But how repair factors are prevented from acting at chromosome ends has been a hotly debated issue. Over the past decade, several telomeric complexes and structures have been identified and proposed to protect chromosome ends, but conclusive evidence that any of these are required for protection has been lacking.
“We set out to define the minimal requirements that would allow the DNA repair machinery to distinguish a chromosome end from a break,” said Dr. Baumann. “By establishing an in vitro assay for chromosome end protection and by implicating specific proteins, we have opened the door to elucidate the mechanism by which RAP1/TRF2 inhibits double-strand break repair at chromosome ends.”
“These findings are important for establishing a better understanding of tumor development,” said Robb Krumlauf, Ph.D., Scientific Director. “Genomic instability and gross chromosomal rearrangements are a hallmark of cancer cells. The mechanisms that initiate and drive these events are only poorly understood, but it is widely accepted that loss of chromosome end protection can initiate genomic instability through bridge-breakage-fusion cycles. It is, therefore, very important to understand the mechanism of chromsome end protection and how and why it fails during tumorigenesis.”
Dr. Baumann, who received a Pew Scholar Award in 2003 and a Basil O’Connor Scholar Award in 2004, holds an academic appointment as an Assistant Professor in the Department of Biochemistry & Molecular Biology at The University of Kansas School of Medicine. To learn more about the work of the Baumann Lab, visit http://www.stowers-institute.org/labs/BaumannLab.asp.
About the Stowers Institute
Housed in a 600,000 square-foot state-of-the-art facility on a 10-acre campus in the heart of Kansas City, Missouri, the Stowers Institute for Medical Research conducts basic research on fundamental processes of cellular life. Through its commitment to collaborative research and the use of cutting-edge technology, the Institute seeks more effective means of preventing and curing disease. The Institute was founded by Jim and Virginia Stowers, two cancer survivors who have created combined endowments of $2 billion in support of basic research of the highest quality.
Marie Jennings | EurekAlert!
During HIV infection, antibody can block B cells from fighting pathogens
14.08.2018 | NIH/National Institute of Allergy and Infectious Diseases
First study on physical properties of giant cancer cells may inform new treatments
14.08.2018 | Brown University
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur
What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...
The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.
Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...
08.08.2018 | Event News
27.07.2018 | Event News
25.07.2018 | Event News
14.08.2018 | Information Technology
14.08.2018 | Life Sciences
14.08.2018 | Life Sciences