Around the home, regularly used tools are generally kept close at hand: a can opener in a kitchen drawer, a broom in the hall closet. Less frequently used tools are more likely to be stored in less accessible locations, out of immediate reach, perhaps in the basement or garage. And hazardous tools might even be kept under lock and key.
Similarly, the human genome has developed a set of sophisticated mechanisms for keeping selected genes readily available for use while other genes are kept securely stored away for long periods of time, sometimes forever. Candidate genes for such long-term storage include those required only for early development and proliferation, potentially dangerous genes that could well trigger cancers and other disorders should they be reactivated later in life. Cancer researchers and others have been eager to learn more about the molecules that direct this all-important system for managing the genome.
Now, researchers at The Wistar Institute and Fox Chase Cancer Center have successfully determined the three-dimensional structure of a key two-molecule complex involved in long-term gene storage, primarily in cells that have ceased proliferating, or growing. The study also sheds light on a related two-molecule complex that incorporates one member of the molecular pair, but with a different partner. This second complex is involved in storing genes in a more accessible way in cells that continue to grow. A report on the team's findings, published online on September 17, will appear in the October issue of Nature Structural and Molecular Biology.
"The two-molecule complex we studied is pivotal for protecting certain genes from expression, genes that could cause problems if they were activated," says Ronen Marmorstein, Ph.D., a professor in the Gene Expression and Regulation Program at Wistar and one of the two senior authors on the study. "This is the first time we've been able to see the structure of these molecules communicating and interacting with each other, and it provides important insights into their function."
"By defining some of the rules that dictate how these complexes are formed and operate, we have revealed a part of the difference between growing and non-growing cells," says Peter D. Adams, Ph.D., an associate member in the Basic Science Division at Fox Chase and the other senior author on the study. "This difference is crucial to the distinction between normal and cancerous cells and may inform our ability to treat this disease."
The molecular complex studied by the scientists governs the assembly of an especially condensed form of chromatin, the substructure of chromosomes. The complex is called a histone chaperone complex, responsible for inserting the appropriate histones into the correct locations within the chromatin. Histones are relatively small proteins around which DNA is coiled to create structures called nucleosomes. Compact strings of nucleosomes, then, form into chromatin.
"There are more and less condensed forms of chromatin," explains Marmorstein. "The less condensed forms correlate with more gene expression, and the more condensed forms involve DNA that's buried away and is not transcribed."
"Appropriate packaging of the DNA in the cell nucleus is crucial for proper functioning of the cell and suppression of disease states, such as cancer," says Adams.
An unanticipated observation from the study centers on the region of association between the two molecules in the complex. The researchers knew that one of the two molecules in the complex, called ASF1, associated with a particular molecular partner, HIRA, when directing assembly of the more condensed form of chromatin. But it could also associate with a different partner, called CAF1, to shepherd assembly of the less condensed form of chromatin.
On closer study, the scientists discovered that HIRA and CAF1 have nearly identical structural motifs in the regions of interaction with ASF1. This means that ASF1 can bind to one or the other molecular partner, but not to both. In other words, the interaction is mutually exclusive: A kind of decision is made by ASF1 as to whether to guide the assembly process towards the more or less condensed forms of chromatin. What determines the choice? The relevant factors are unknown for now.
Franklin Hoke | EurekAlert!
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy