Featured Research

from universities, journals, and other organizations

Two unsuspected proteins may hold the key to creating artificial chromosomes

Date:
April 28, 2011
Source:
Whitehead Institute for Biomedical Research
Summary:
Scientists report that two proteins once thought to have only supporting roles, are the true "stars" of the kinetochore assembly process in human cells. The kinetochore is vital to proper DNA distribution during cell division. This finding suggests that scientists may be able to stimulate kinetochore assembly in a process that could lead to new genetic research tools, such as efficient creation of artificial human chromosomes.

Whitehead Institute scientists report that two proteins, once thought to have only supporting roles, are the true "stars" of the kinetochore assembly process in human cells.

Related Articles


The kinetochore is vital to proper DNA distribution during cell division. This finding suggests that scientists may be able to stimulate kinetochore assembly in a process that could lead to new genetic research tools, such as efficient creation of artificial human chromosomes.

"When you understand a process really well, then it can become a tool. And I think this is a nice example of that," says Whitehead Member Iain Cheeseman. "We now fundamentally understand something about the way kinetochore specification and assembly works. And because we understand that, now one could imagine it being used as a tool."

For many years scientists have understood the kinetochore's role in cell division but did not know how its individual parts came together during this process. At the beginning of cell division, the kinetochore consists of a few proteins associated with a chromosome's centromere, which is the section where the arms of an X-shaped chromosome join. As cell division progresses, additional kinetochore proteins attach at the centromere, ultimately forming a complete kinetochore complex consisting of about 100 proteins. At this point, one kinetochore is partially integrated into each lengthwise half of the chromosome, called a sister chromatid; a chromosome's sister chromatids are identical copies of the same piece of DNA.

To distribute the sister chromatids between the two future cells, long protein filaments from opposite sides of the cell reach out, latch onto the chromatids' kinetochores, and begin pulling on them until the sister chromatids split apart. Then, the chromatids are dragged to opposite sides of the cell, ensuring that the future cells will each have a copy of this piece of DNA.

To identify which proteins are necessary for a kinetochore to self-assemble, Karen Gascoigne, a postdoctoral researcher in the Cheeseman lab, positioned three of them on the chromatids' DNA and away from their normal location on the centromere. By moving the proteins away from their normal position, Gascoigne isolated the effects of each protein from potential interactions with the centromere and highlighted the capabilities attributable only to that protein.

The first protein, called CENP-A, is essential for identifying where the kinetochore should locate, and many scientists thought it was vital to kinetochore assembly. However, when Gascoigne moved CENP-A away from the centromere, only a few kinetochore components were recruited to attach onto CENP-A, showing that this protein is not responsible for assembling an entire kinetochore.

When Gascoigne moved the proteins CENP-C and CENP-T away from the centromere, the two proteins attracted almost all of the kinetochore proteins to their location and fostered assembly of a makeshift kinetochore capable of separating sister chromatids.

"So that tells us that these two proteins are essential and sufficient to build the kinetochore even in the absence of CENP-A," says Gascoigne, who reports her findings in the April 29 issue of Cell. "Which is unexpected and very exciting. This tells us a lot about how kinetochores are put together in the cell."

This new ability to form a kinetochore anywhere on DNA may be particularly useful for creating artificial human chromosomes. These collections of genes could be used in research to insert new genes into a cell. Currently, scientists insert genes by infecting cells with a virus that haphazardly inserts the DNA into the cells' genomes, a process that can corrupt essential genes and possibly kill cells.

Artificial chromosomes circumvent this potential damage. But their widespread use is thwarted by scientists' current inability to outfit artificial chromosomes with kinetochores. Without kinetochore complexes for those long protein filaments to latch onto during cell division, the artificial chromosomes cannot be passed from the original cells to subsequent generations, meaning that the artificial chromosomes' traits are lost.

By perfecting kinetochore assembly using just CENP-C and CENP-T, Gascoigne is working to overcome this shortcoming in artificial human chromosomes.

"We're interested to see if you can bypass having a centromere by putting in just these two proteins into the artificial chromosome," says Gascoigne. "And then the cell would build the kinetochore itself, which will allow the artificial chromosome to segregate during cell division."

This research was supported by the Massachusetts Life Sciences Center, the Searle Scholars Program, and the National Institutes of Health/National Institute of General Medical Sciences.


Story Source:

The above story is based on materials provided by Whitehead Institute for Biomedical Research. The original article was written by Nicole Giese. Note: Materials may be edited for content and length.


Journal Reference:

  1. Karen E. Gascoigne, Kozo Takeuchi, Aussie Suzuki, Tetsuya Hori, Tatsuo Fukagawa and Iain M. Cheeseman. Induced ectopic kinetochore assembly bypassing the requirement for CENP-A nucleosomes. Cell, April 29, 2011 DOI: 10.1016/j.cell.2011.03.031

Cite This Page:

Whitehead Institute for Biomedical Research. "Two unsuspected proteins may hold the key to creating artificial chromosomes." ScienceDaily. ScienceDaily, 28 April 2011. <www.sciencedaily.com/releases/2011/04/110428123944.htm>.
Whitehead Institute for Biomedical Research. (2011, April 28). Two unsuspected proteins may hold the key to creating artificial chromosomes. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2011/04/110428123944.htm
Whitehead Institute for Biomedical Research. "Two unsuspected proteins may hold the key to creating artificial chromosomes." ScienceDaily. www.sciencedaily.com/releases/2011/04/110428123944.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Navy Unveils Robot Fish

Navy Unveils Robot Fish

Reuters - Light News Video Online (Dec. 18, 2014) The U.S. Navy unveils an underwater device that mimics the movement of a fish. Tara Cleary reports. Video provided by Reuters
Powered by NewsLook.com
Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
Dads-To-Be Also Experience Hormone Changes During Pregnancy

Dads-To-Be Also Experience Hormone Changes During Pregnancy

Newsy (Dec. 18, 2014) A study from University of Michigan researchers found that expectant fathers see a decrease in testosterone as the baby's birth draws near. Video provided by Newsy
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