Featured Research

from universities, journals, and other organizations

DNA packaging discovery reveals principles by which CRC mutations may cause cancer

Date:
November 17, 2012
Source:
University of Utah Health Sciences
Summary:
A new discovery concerning a fundamental understanding about how DNA works will produce a "180-degree change in focus" for researchers who study how gene packaging regulates gene activity, including genes that cause cancer and other diseases.

A new discovery from researchers at Huntsman Cancer Institute (HCI) at the University of Utah concerning a fundamental understanding about how DNA works will produce a "180-degree change in focus" for researchers who study how gene packaging regulates gene activity, including genes that cause cancer and other diseases.

Related Articles


The discovery, by Bradley R. Cairns, PhD, Senior Director of Basic Science at HCI and a professor in the Department of Oncological Sciences, is reported in this week's online issue of the journal Nature.

Cairns's research focuses on chromatin remodeling complexes (CRCs), which are cellular protein complexes that behave like motors, expanding or compacting different portions of DNA to either express or silence genes, respectively. Before, scientists thought that the motor within CRCs waits at rest until it receives instructions. Cairns and co-author Cedric R. Clapier show that the motor within a key CRC responsible for gene packaging and assembly is intrinsically turned on, and instead requires specific instructions to turn it off.

"Many articles in the research literature show that CRCs are mutated in cancer cells. They are intimately involved in regulating gene expression -- responsible for correctly packaging genes that control growth proliferation and for unpackaging tumor suppressors," said Cairns. "This research reveals principles by which CRC mutations could cause cancer."

Chromosomes are made of long DNA strands compressed around nodes of protein called nucleosomes; when DNA is compressed, the genes in that area are turned off. Some CRCs, called disassembly CRCs, act as motors that unwind sections of DNA chains, making genes active for a given cell process. Another type, called assembly CRCs, rewinds the DNA chain, recompressing it when the process is complete. The unwind-rewind cycle is repeated continuously throughout a cell's life.

In this study, Cairns and Clapier focused on assembly CRCs. "Before this research, we thought that the motor was off unless a protein coming from another part of the cell turned it on," said Cairns. "Researchers have been searching for the switch by looking at the CRC motor to see what binds to it.

"As it turns out, we discovered that the CRC motor already carries on its flank a 'switch' that inhibits its action until a marker sequence, located on the nucleosome, is encountered. The marker flips the inhibitor switch and allows the CRC to crank the DNA chain back around the nucleosome, promoting gene packaging and silencing" Cairns said. "Our results change where future researchers should be looking to understand how CRCs are regulated -- not at the CRC motor itself, but at the 'switches' that flank the motor."

The study also describes a measuring function on the CRC that checks for the correct distance between one nucleosome and the next, telling the motor to switch off at the proper time, a function needed for gene silencing.

Cairns's lab will now examine this same switching concept in disassembly remodelers. "There are additional remodeler families with alternative functions, like DNA repair," said Cairns. "We think this concept will apply to them as well."

This research was supported by funding from the National Institutes of Health (GM60415 and CA042014) and from the Howard Hughes Medical Institute.


Story Source:

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


Journal Reference:

  1. Cedric R. Clapier, Bradley R. Cairns. Regulation of ISWI involves inhibitory modules antagonized by nucleosomal epitopes. Nature, 2012; DOI: 10.1038/nature11625

Cite This Page:

University of Utah Health Sciences. "DNA packaging discovery reveals principles by which CRC mutations may cause cancer." ScienceDaily. ScienceDaily, 17 November 2012. <www.sciencedaily.com/releases/2012/11/121117184658.htm>.
University of Utah Health Sciences. (2012, November 17). DNA packaging discovery reveals principles by which CRC mutations may cause cancer. ScienceDaily. Retrieved January 31, 2015 from www.sciencedaily.com/releases/2012/11/121117184658.htm
University of Utah Health Sciences. "DNA packaging discovery reveals principles by which CRC mutations may cause cancer." ScienceDaily. www.sciencedaily.com/releases/2012/11/121117184658.htm (accessed January 31, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, January 31, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC: Get Vaccinated for Measles

CDC: Get Vaccinated for Measles

Reuters - US Online Video (Jan. 30, 2015) The CDC is urging people to get vaccinated for measles amid an outbreak that began at Disneyland and has now infected more than 90 people. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Obama To Outline New Plan For Personalized Medicine

Obama To Outline New Plan For Personalized Medicine

Newsy (Jan. 30, 2015) President Obama is expected to speak with drugmakers Friday about his Precision Medicine Initiative first introduced last week. Video provided by Newsy
Powered by NewsLook.com
NFL Concussions Down; Still on Parents' Minds

NFL Concussions Down; Still on Parents' Minds

AP (Jan. 30, 2015) The NFL announced this week that the number of game concussions dropped by a quarter over last season. Still, the dangers of the sport still weigh on players, and parents&apos; minds. (Jan. 30) Video provided by AP
Powered by NewsLook.com
U.S. Wants to Analyze DNA from 1 Million People

U.S. Wants to Analyze DNA from 1 Million People

Reuters - US Online Video (Jan. 30, 2015) The U.S. has proposed analyzing genetic information from more than 1 million American volunteers to learn how genetic variants affect health and disease. Rough Cut (no reporter narration). Video provided by Reuters
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


Health & Medicine

Mind & Brain

Living & Well

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