Scientists at Emory University School of Medicine have caught in action one of the tools mammalian cells use to maintain their pattern of methylation. Visualized by X-ray crystallography, the SRA domain of the protein UHRF1 appears to act like a bookmark while enzymes are copying a molecule of DNA.
The team's description of the protein's structure while bound to DNA is published this week in Nature.
Scientists refer to methylation, the addition of a methyl group to DNA, as an "epigenetic" modification because it adds a layer of information on top of the genetic sequence of the DNA itself. It marks genes for silencing, which means they do not manufacture proteins.
"The processes that copy the methylation pattern have to be faithful," says senior author Xiaodong Cheng, PhD, professor of biochemistry and a Georgia Research Alliance eminent scholar. "Otherwise, losing DNA methylation marks can have serious consequences, causing genes to become active at the wrong places and times."
"Gene silencing via DNA methylation is critical for normal development and for curbing the runaway cell division that characterizes cancer," said Peter Preusch, PhD, who oversees biophysics grants at the National Institute of General Medical Sciences of the National Institutes of Health. "Alterations in methylation patterns are also important for generating embryonic stem-like cells from differentiated cells."
In mammalian cells, methylation usually appears on double stranded DNA where the nucleotide Cytosine (C) is followed by Guanine (G). The complementary sequence on the opposite strand is also C then G, and the methylation appears on both Cs.
When a cell is copying its DNA, a set of enzymes duplicates the DNA sequence from the parental strand to the new "daughter" strand but not the methylation. Each new daughter strand of the DNA molecule is left with the previously methylated Cs unmethylated. UHRF1 recognizes this "hemi-methylated" DNA and calls in a methyltransferase enzyme to add a second methyl group onto the daughter strand.
"UHRF1 has the important task of making sure the methyltransferase enzyme does its job in the right place and right time," Cheng says.
Mouse cells that have deleted the UHRF1 gene are more sensitive to DNA-damaging agents such as radiation, and mouse embryos without the gene cannot complete development. Other studies have found that cancer cells produce more UHRF1 than non-cancerous cells.
What was an unexpected finding was how the SRA domain of UHRF1 recognizes the hemi-methylated DNA, Cheng says. It flips the methylated nucleotide out of the DNA helix, which only had been seen previously in enzymes that physically modify the DNA.
Cheng says the flipping mechanism could prevent the protein from sliding away once it has found a hemi-methylated site.
"It suggests that it serves as a placeholder, where it recruits other enzymes for faithful DNA methylation or repair enzymes if the DNA has been damaged," he says.
Holly Korschun | 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