Featured Research

from universities, journals, and other organizations

DNA Editing Tool Flips Its Target

Date:
September 5, 2008
Source:
Emory University
Summary:
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 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.

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.

The first author of the paper is postdoctoral fellow Hideharu Hashimoto.

Contributions also came from Emory assistant professors of biochemistry John Horton and Xing Zhang, and postdoctoral fellow Magnolia Bostick and professor of molecular, cell and developmental biology Steven Jacobsen, both from University of California, Los Angeles.

The research was funded by the National Institutes of Health, the Howard Hughes Medical Institute and the Georgia Research Alliance.


Story Source:

The above story is based on materials provided by Emory University. Note: Materials may be edited for content and length.


Cite This Page:

Emory University. "DNA Editing Tool Flips Its Target." ScienceDaily. ScienceDaily, 5 September 2008. <www.sciencedaily.com/releases/2008/09/080903134213.htm>.
Emory University. (2008, September 5). DNA Editing Tool Flips Its Target. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2008/09/080903134213.htm
Emory University. "DNA Editing Tool Flips Its Target." ScienceDaily. www.sciencedaily.com/releases/2008/09/080903134213.htm (accessed October 22, 2014).

Share This



More Plants & Animals News

Wednesday, October 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Working Mother DIY: Pumpkin Pom-Pom

Working Mother DIY: Pumpkin Pom-Pom

Working Mother (Oct. 22, 2014) How to make a pumpkin pom-pom. Video provided by Working Mother
Powered by NewsLook.com
San Diego Zoo's White Rhinos Provide Hope for the Critically Endangered Species

San Diego Zoo's White Rhinos Provide Hope for the Critically Endangered Species

Reuters - Light News Video Online (Oct. 22, 2014) The pair of rare white northern rhinos bring hope for their species as only six remain in the world. Elly Park reports. Video provided by Reuters
Powered by NewsLook.com
Raw: Bear Cub Strolls Through Oregon Drug Store

Raw: Bear Cub Strolls Through Oregon Drug Store

AP (Oct. 22, 2014) Shoppers at an Oregon drug store were surprised by a bear cub scurrying down the aisles this past weekend. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Family Pleads for Pet Pig to Stay at Home

Family Pleads for Pet Pig to Stay at Home

AP (Oct. 22, 2014) The Johnson family lost their battle with the Chesterfield County, Virginia Planning Commission to allow Tucker, their pet pig, to stay in their home, but refuse to let the board keep Tucker away. (Oct. 22) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins