Navigation Links
DNA editing tool flips its target

Imagine having to copy an entire book by hand without missing a comma. Our cells face a similar task every time they divide. They must duplicate both their DNA and a subtle pattern of punctuation-like modifications on the DNA known as methylation.

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.


Contact: Holly Korschun
Emory University

Related medicine news :

1. Abnormal editing of gene messages may be a cause of lupus
2. Innate immune system targets asthma-linked fungus for destruction
3. World Cancer Declaration sets ambitious targets for 2020
4. New Vitamin Targets Needs of Nurses
5. Targeted radiation therapy can control limited cancer spread
6. Targeted drug therapy found effective in patients with common form of immune-mediated kidney disease
7. Align Technology Targets Mainstream Orthodontics Market With Invisalign Teen(TM)
8. Lung Cancer Trial Targets Asbestos-Related Disease
9. Breakthrough "Neuro Nutrition" Targets the Brain and Vagus Nerve To Boost the Body's Immune, Hormone and Neurological Systems
10. Multi-target immune therapy improves outcomes of severe lupus nephritis
11. Researchers identify promising cancer drug target in prostate tumors
Post Your Comments:
(Date:11/27/2015)... ... 27, 2015 , ... A simply groundbreaking television series, "Voices in America", which ... into an array of issues that are presently affecting Americans. Dedicated to providing the ... show is changing the subjects consumers focus on, one episode at a time. ...
(Date:11/27/2015)... ... November 27, 2015 , ... The men and ... nonprofit healthcare organizations in the country. They have overseen financial turnarounds, shown commitment ... advance the healthcare industry as a whole through their advocacy and professional efforts. ...
(Date:11/26/2015)... ... November 26, 2015 , ... ... in central Michigan, have come together on Thanksgiving Day to share the things ... for viewing on the Serenity Point YouTube channel, patients displayed what they wrote ...
(Date:11/26/2015)... ... , ... The Catalent Applied Drug Delivery Institute today announced ... form selection in early phase drug development. The first of these is to ... the UK’s emerging life sciences companies, corporate partners, and investors, at Milton Park, ...
(Date:11/26/2015)... CA (PRWEB) , ... November 26, 2015 , ... ... a new set of retro-fused, self-animating trailer titles with ProTrailer: Vintage. This newly ... options. These classically-influenced trailer titles work with any font, giving users limitless opportunities ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... , November 26, 2015 ... "Self Administration of High Viscosity Drugs" ... ) has announced the addition of the ... to their offering. --> Research and ... of the "Self Administration of High Viscosity ...
(Date:11/26/2015)... DUBLIN , November 26, 2015 /PRNewswire/ ... the addition of the "Radioimmunoassay Market ... User (Hospital, Pharmaceutical Industry, Academics, Clinical Diagnostic ... - Global Forecast to 2020" report ... ) has announced the addition of the ...
(Date:11/25/2015)... , Nov. 25, 2015 ... the addition of the "Global Brain ... their offering. --> ) ... "Global Brain Monitoring Devices Market 2015-2019" ... Research and Markets ( ) has ...
Breaking Medicine Technology: