Featured Research

from universities, journals, and other organizations

Experiments decipher key piece of the ‘histone code’ in cell division

Date:
September 22, 2010
Source:
Rockefeller University
Summary:
Reproduce or perish. That's the bottom line for genes. Because nothing lives forever, reproduction is how life sustains itself, and it happens most fundamentally in the division and replication of the cell, known as mitosis. Now new research has detailed a key role in mitosis for a chemical modification to histone proteins that package lengthy strings of DNA into compact chromosomes. The experiments, recently published in Science, add to an increasingly intricate picture of the precisely timed events that separate new copies of chromosomes to opposite ends of a cell just before the cell divides, one of the most fundamental processes involved in the reproduction of life.

Modify and divide. New research suggests a chemical modification to the DNA packaging protein site H3T3 (purple) is necessary for the recruitment of the chromosomal passenger complex (green) which helps segregate chromosomes in preparation for cell division.
Credit: Image courtesy of Rockefeller University

Reproduce or perish. That's the bottom line for genes. Because nothing lives forever, reproduction is how life sustains itself, and it happens most fundamentally in the division and replication of the cell, known as mitosis. Now new research at Rockefeller University has detailed a key role in mitosis for a chemical modification to histone proteins that package lengthy strings of DNA into compact chromosomes. The experiments, recently published in Science, add to an increasingly intricate picture of the precisely timed events that separate new copies of chromosomes to opposite ends of a cell just before the cell divides, one of the most fundamental processes involved in the reproduction of life.

"We've known that histones become decorated during mitosis for more than 30 years, but we haven't really understood their function," says Hironori Funabiki, head of the Laboratory of Chromosome and Cell Biology. "Now we've finally decoded exactly how one of these marks works."

Funabiki says the findings provide hard evidence for the "histone code hypothesis," advanced by Rockefeller's C. David Allis and colleagues, which suggests that combinations of histone modifications attract or remove specific proteins, controlling the immediate environment of chromosomes in the cell. The orchestration of the exact timing and localization of the vast array of molecules and processes involved in reproducing the chromosomes is one of the basic wonders of biology and is at the core of both healthy living and diseases such as cancer, that arise when the process goes awry.

Funabiki, postdoctoral associate Alex Kelly, graduate student Cristina Ghenoiu and their colleagues focused on the addition of a phosphate group to histone H3 at the site theronine 3 (H3T3); it was first identified in 1980, but its function has remained a mystery. The researchers built on their previous work singling out the chromosomal passenger complex, a group of proteins in the cell that includes the enzyme Aurora B. This complex must be brought to chromosomes and activated to facilitate the assembly of cellular scaffolding called spindle microtubules, which are required to separate chromosomes in a dividing cell. In a series of new experiments, they showed that another member of the complex, Survivin (it's highly similar to a class of proteins known to stem the process of programmed cell death, or apoptosis) recognizes the phosphate group at H3T3 and, in turn, activates Aurora B.

The researchers found that the phosphate group must be removed after the chromosomes are segregated so that the chromosomes can be properly repackaged to repeat the process over again, and they showed that the enzyme Haspin plays a role in adding the phosphate group that Survivin recognizes and is necessary for the chain of events to come off smoothly. Since both Survivin and Aurora B have been implicated in many cancers, molecules that disrupt the interaction between histone H3 and Survivin could allow for a new avenue for targeted therapeutics.

The study also shows that how Survivin recognizes H3T3 phosphorylation is very similar to how "inhibitor of apoptosis" proteins (IAPs) bind to their own ligands, whose mimetics have been investigated as anti-cancer drugs. "It brings a lot of fields together. I think it will be exciting to a lot of people working on epigenetics, apoptosis and the cell cycle," Kelly says. "We cracked one code," Funabiki says, "but there are yet many to be decoded to understand how chromosomes orchestrate mitosis."


Story Source:

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


Journal Reference:

  1. A. E. Kelly, C. Ghenoiu, J. Z. Xue, C. Zierhut, H. Kimura, H. Funabiki. Survivin Reads Phosphorylated Histone H3 Threonine 3 to Activate the Mitotic Kinase Aurora B. Science, 2010; DOI: 10.1126/science.1189505

Cite This Page:

Rockefeller University. "Experiments decipher key piece of the ‘histone code’ in cell division." ScienceDaily. ScienceDaily, 22 September 2010. <www.sciencedaily.com/releases/2010/09/100920211118.htm>.
Rockefeller University. (2010, September 22). Experiments decipher key piece of the ‘histone code’ in cell division. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2010/09/100920211118.htm
Rockefeller University. "Experiments decipher key piece of the ‘histone code’ in cell division." ScienceDaily. www.sciencedaily.com/releases/2010/09/100920211118.htm (accessed July 25, 2014).

Share This




More Plants & Animals News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Boy Attacked by Shark in Florida

Boy Attacked by Shark in Florida

Reuters - US Online Video (July 24, 2014) An 8-year-old boy is bitten in the leg by a shark while vacationing at a Florida beach. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Goma Cheese Brings Whiff of New Hope to DRC

Goma Cheese Brings Whiff of New Hope to DRC

Reuters - Business Video Online (July 24, 2014) The eastern region of the Democratic Republic of Congo, mainly known for conflict and instability, is an unlikely place for the production of fine cheese. But a farm in the village of Masisi, in North Kivu is slowly transforming perceptions of the area. Known simply as Goma cheese, the Congolese version of Dutch gouda has gained popularity through out the region. Ciara Sutton reports. Video provided by Reuters
Powered by NewsLook.com
Tyrannosaur Pack-Hunting Theory Aided By New Footprints

Tyrannosaur Pack-Hunting Theory Aided By New Footprints

Newsy (July 24, 2014) A new study claims a set of prehistoric T-Rex footprints supports the theory that the giant predators hunted in packs instead of alone. Video provided by Newsy
Powered by NewsLook.com
Bill Gates: Health, Agriculture Key to Africa's Development

Bill Gates: Health, Agriculture Key to Africa's Development

AFP (July 24, 2014) Health and agriculture development are key if African countries are to overcome poverty and grow, US software billionaire Bill Gates said Thursday, as he received an honourary degree in Ethiopia. Duration: 00:36 Video provided by AFP
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:
from the past week

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