A landmark study to be published in the October 30, 2014 print edition of the journal Nature provides new insight into the function of an enzyme related to the BRCA1 breast cancer protein. The study by a team at Penn State University is the first to produce a detailed working image of an enzyme in the Polycomb Repressive Complex 1 (PRC1) -- a group that regulates cell development and is associated with many types of cancer.
Enzymes like PRC1 turn on or turn off the activity of genes in a cell by manipulating individual chromosome units called nucleosomes. "The nucleosome is a key target of the enzymes that conduct genetic processes critical for life," said Song Tan, professor of biochemistry and molecular biology at Penn State University and the leader of the study's research team.
This image is the first detailed picture of the crystal structure of a gene-regulation enzyme while it is working on a nucleosome -- a fundamental component of the chromosomes that provide structure and organization for an organism's genes. Nucleosomes are key targets of the enzymes that conduct genetic processes critical for life. This image reveals the crystal structure of the PRC1 enzyme (yellow, blue and red) bound to the nucleosome (DNA in light blue, histone proteins in purple, light green, light yellow and pink) This image was obtained in the lab of Song Tan at Penn State University and was published in the print edition of the journal Nature on October 30, 2014. Credit: Song Tan lab, Penn State University
This image is the first detailed picture of the crystal structure of a gene-regulation enzyme while it is working on a nucleosome -- a fundamental component of the chromosomes that provide structure and organization for an organism's genes. Nucleosomes are key targets of the enzymes that conduct genetic processes critical for life. This image reveals the crystal structure of the PRC1 enzyme (yellow, blue and red) bound to the nucleosome (DNA in light blue, histone proteins in purple, light green, light yellow and pink) This image was obtained in the lab of Song Tan at Penn State University and was published in the print edition of the journal Nature on October 30, 2014.
Credit: Song Tan lab, Penn State University
The Penn State scientists obtained the first crystal structure of a gene regulation enzyme while it is working on a nucleosome. The image reveals previously unknown information about how the enzyme attaches to its nucleosome target.
Before this study, scientists had been unable to picture exactly how cancer-related enzymes in the PRC1 group interacted with a nucleosome to control gene activity. The study is also the first to determine the crystal structure of a multisubunit protein complex bound to a nucleosome, which itself is a complex assembly of DNA and 4 histone proteins.
The research is the culmination of over 12 years of research by the Tan laboratory to capture an image of this important class of enzymes bound to the nucleosome. His lab earlier had determined the first structure of another nucleosome-bound protein, RCC1.
"This is the second important structure from the Tan lab to date of a nucleosome in complex with a protein known to interact with and modify chromatin behavior, which in turn can influence human gene expression," said Peter Preusch, Ph.D., of the National Institutes of Health's National Institute of General Medical Sciences, which partially funded the research. "Along with Dr. Tan's previous work detailing a nucleosome bound to the key regulatory protein, RCC1, this new structure adds to our knowledge of how proteins can regulate the structure and function of our genetic material."
The research project was proposed and executed by team member Robert K. McGinty, a Damon Runyon postdoctoral fellow at Penn State. McGinty and Ryan C. Henrici, an undergraduate in the Penn State Schreyer Honors College, grew crystals of the PRC1 enzyme bound to the nucleosome.
The team then solved the three-dimensional structure of this large molecular assembly by X-ray crystallography. "We are excited about this crystal structure because it provides new paradigms for understanding how chromatin enzymes function," McGinty said.
The study performed in the Penn State Center for Eukaryotic Gene Regulation provides unexpected insight into the workings of the BRCA1 breast-cancer-associated tumor-suppressor protein. Like PRC1, BRCA1 is a chromatin enzyme that shares a similar activity on the nucleosome. Tan said, “Our study suggests that BRCA1 and PRC1 employ a similar mechanism to anchor to the nucleosome”. Tan and his team now are working to visualize how BRCA1 and other disease-related chromatin enzymes interact with the nucleosome.
This research was supported by grants from the National Institutes of Health, the Damon Runyon Cancer Research Foundation and Penn State University.
Song Tan: firstname.lastname@example.org, 814-865-3355
Barbara Kennedy (PIO): email@example.com, 814-863-4682
Barbara K. Kennedy | EurekAlert!
First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife
Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
25.10.2016 | Earth Sciences
25.10.2016 | Power and Electrical Engineering
25.10.2016 | Process Engineering