Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

First detailed picture of a cancer-related cell enzyme in action on a chromosome unit

30.10.2014

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.

Contacts
Song Tan: sxt30@psu.edu, 814-865-3355
Barbara Kennedy (PIO): science@psu.edu, 814-863-4682

Barbara K. Kennedy | EurekAlert!
Further information:
http://science.psu.edu/news-and-events/2014-news/Tan10-2014-2

More articles from Life Sciences:

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

The interactome of infected neural cells reveals new therapeutic targets for Zika

23.01.2017 | Life Sciences

Melting solid below the freezing point

23.01.2017 | Materials Sciences

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

VideoLinks
B2B-VideoLinks
More VideoLinks >>>