Featured Research

from universities, journals, and other organizations

Two Separate Controls Regulate Chromosome Copying In Yeast

Date:
October 23, 2001
Source:
Johns Hopkins Medical Institutions
Summary:
The crucial job of ensuring that just one copy of a genome gets made during cell division turns out to be shared by two independent "controllers," researchers from Johns Hopkins School of Medicine report in the Oct. 23 issue of the Proceedings of the National Academy of Sciences.

The crucial job of ensuring that just one copy of a genome gets made during cell division turns out to be shared by two independent "controllers," researchers from Johns Hopkins School of Medicine report in the Oct. 23 issue of the Proceedings of the National Academy of Sciences.

In experiments with yeast cells, the scientists discovered that if the two controller proteins remain in the cell then copying continues abnormally. Normally, the proteins are destroyed after a single copy, or replication, of the DNA is made.

"We knew these proteins were required for DNA replication and that they normally went away after one DNA copy was made, but we didn't know whether their disappearance was important for controlling the duplication of the genome," says Thomas Kelly, M.D., Ph.D., professor and director of molecular biology and genetics and director of the Institute for Basic Biomedical Sciences. "Now we know that DNA replication ceases because these two proteins are destroyed."

Understanding this complex and tightly regulated process may help clarify what goes wrong in cancer cells, say the researchers. The yeast used in the experiment (Schizosaccharomyces pombe) divides by splitting into two new cells, each with a copy of the organism's entire genome, in a process very similar to that of human cells.

"In human cells, for reasons still largely unknown, some cells ultimately acquire enough genetic mutations to cause cancer, despite having different ways to prevent, find and fix problems in the genome," says Mark Frattini, M.D., Ph.D., a postdoctoral fellow in the department of medical oncology and the department of molecular biology and genetics, which is part of the school's Institute for Basic Biomedical Sciences. "We can't yet link these two controller proteins in yeast or their human counterparts to cancer, but we do have a new genome control pathway to examine."

In the yeast, one controller, the Cdc18 protein, helps build machinery that copies DNA, and the other, Cdt1, helps start that machine. The levels of both proteins normally rise before DNA replication and fall once it's completed.

By disrupting the yeasts' ability to regulate the levels of Cdc18 and Cdt1, the Hopkins scientists proved that the normal destruction of the two proteins restricts DNA replication to a single copy. In cells with mutant Cdc18 and Cdt1 whose levels never drop, DNA replication keeps going.

"Having two proteins offers redundant protection against making extra copies of DNA, which helps maintain the integrity of the genome for subsequent generations of cells," says Frattini.

The scientists used a version of the gene for Cdc18 that would produce normal amounts of an altered protein that could not be marked for destruction, but which would otherwise function normally. In the case of Cdt1, the scientists created two new versions of the gene, both of which were controlled by an "on switch" that the researchers, but not the cell, could manipulate.

The mutations worked as expected: the levels of Cdc18 and the Cdt1 proteins no longer varied normally. Cdc18 levels increased when the cell began constructing the DNA copier, as normal, but then remained high. And all cells produced Cdt1, regardless of their point in cell division.

The amount of DNA in the cells reflected the changes' effects on the DNA copier. Many cells with the mutant Cdc18 and Cdt1 contained as much as two to four times the amount of DNA they should have, says Frattini. Cells with just one of the proteins altered were normal.

Other researchers have found that very large amounts of indestructible Cdc18 could lead to extra replication of DNA in the yeast, but Hopkins' experiments show that if protein levels are closer to normal, both Cdc18 and Cdt1 are required to continue DNA copying.

In addition to Kelly and Frattini, co-authors are first author Vidya Gopalakrishnan, Pamela Simancek and Christopher Houchens of The Johns Hopkins University School of Medicine, Hilary Snaith formerly of The Salk Institute and now at the University of Edinburgh, UK, and Shelley Sazer of the Baylor College of Medicine.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Cite This Page:

Johns Hopkins Medical Institutions. "Two Separate Controls Regulate Chromosome Copying In Yeast." ScienceDaily. ScienceDaily, 23 October 2001. <www.sciencedaily.com/releases/2001/10/011023072415.htm>.
Johns Hopkins Medical Institutions. (2001, October 23). Two Separate Controls Regulate Chromosome Copying In Yeast. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2001/10/011023072415.htm
Johns Hopkins Medical Institutions. "Two Separate Controls Regulate Chromosome Copying In Yeast." ScienceDaily. www.sciencedaily.com/releases/2001/10/011023072415.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

Cadaver Dogs Aid Search for More Victims of Suspected Indiana Serial Killer

Cadaver Dogs Aid Search for More Victims of Suspected Indiana Serial Killer

Reuters - US Online Video (Oct. 21, 2014) Police in Gary, Indiana are using cadaver dogs to search for more victims after a suspected serial killer confessed to killing at least seven women. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
White Lion Cubs Unveiled to the Public

White Lion Cubs Unveiled to the Public

Reuters - Light News Video Online (Oct. 21, 2014) Visitors to Belgrade zoo meet a pair of three-week-old lion cubs for the first time. Tara Cleary reports. Video provided by Reuters
Powered by NewsLook.com
'Cadaver Dog' Sniffs out Human Remains

'Cadaver Dog' Sniffs out Human Remains

AP (Oct. 21, 2014) Where's a body buried? Buster's nose can often tell you. He's a cadaver dog, specially trained to find human remains and increasingly being used by law enforcement and accepted in courts. These dogs are helping solve even decades-old mysteries. (Oct. 21) Video provided by AP
Powered by NewsLook.com
White Lion Cubs Born in Belgrade Zoo

White Lion Cubs Born in Belgrade Zoo

AFP (Oct. 20, 2014) Two white lion cubs, an extremely rare subspecies of the African lion, were recently born at Belgrade Zoo. They are being bottle fed by zoo keepers after they were rejected by their mother after birth. Duration: 00:42 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:

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