In plants, animals and other "eukaryotes," the assembly of a multi-protein complex called pre-replicative complex (preRC) is the first step in the initiation of DNA replication. As the name implies, origin recognition complex (ORC) proteins bind to origins of DNA replication.
Subsequently, other components of preRC are assembled at these sites. In addition to its role in DNA replication, ORC is also involved in gene silencing and organization of the tightly packed DNA, called heterochromatin. How ORC is brought to the DNA in human cells had previously remained a mystery.
Researchers at the University of Illinois, led by Professor Supriya Prasanth from the school of molecular and cellular biology, have identified a novel protein that is highly conserved in higher eukaryotes. They have shown that in human cells, this protein (once known as LRWD1 but renamed ORCA, for "ORC-associated" protein) associates with ORC and shows similar cell cycle dynamics to ORC. Along with ORC, this protein binds to heterochromatic structures, including centromeres and telomeres, which are important to cell division and chromosome maintenance.
The researchers further demonstrated that ORCA efficiently recruits ORC to chromatin, the DNA and proteins that make up the chromosome. Depletion of ORCA in human primary cells as well as in embryonic stem cells results in the loss of ORC binding to chromatin and subsequent arrest of cells in a vital phase of the cell cycle. Loss of ORCA results in defects in cellular proliferation, suggesting that a fine-tuned balance in the levels of ORCA is maintained in a normal cell. These results suggest that a novel protein, ORCA, is critical for initiation of DNA replication and heterochromatin organization in mammalian cells.
This work appears in the October 8, 2010 issue of the journal Molecular Cell.
"The discovery of this new protein is going to be revolutionary in the field of replication and cell cycle," Prasanth said. "We all know that diseases like cancer are caused by uncontrolled proliferation of cells, and our data demonstrates that ORCA controls proliferation of cells. This work is going to have important implications in cancer biology."
The study was spearheaded by Zhen Shen, a graduate student, with assistance from post-doctoral fellows Kizhakke M. Sathyan and Arindam Chakraborty. Other Illinois researchers on the study include Kannanganattu Prasanth, a professor in the department of cell and developmental biology; his graduate student Ruiping Zheng; Brian Freeman, a professor in the department of cell and developmental biology; Fei Wang, a professor in cell and developmental biology; and his graduate student Yejie Geng. The funding for this study was provided by National Science Foundation, and The Leukemia and Lymphoma Society, through a Special Fellow Award granted to Supriya Prasanth.
William Gillespie | EurekAlert!
CWRU researchers find a chemical solution to shrink digital data storage
22.06.2017 | Case Western Reserve University
Warming temperatures threaten sea turtles
22.06.2017 | Swansea University
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.
New Manufacturing Technologies for New Products
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
22.06.2017 | Materials Sciences
22.06.2017 | Information Technology
22.06.2017 | Medical Engineering