Featured Research

from universities, journals, and other organizations

DNA replication protein also has a role in mitosis, cancer

Date:
May 13, 2012
Source:
University of North Carolina School of Medicine
Summary:
Scientists have discovered that a protein known as Cdt1, which is required for DNA replication, also plays an important role in a later step of the cell cycle, mitosis. The finding presents a possible explanation for why so many cancers possess not just genomic instability, but also more or less than the usual 46 DNA-containing chromosomes.

Mitotic spindle-chromosome attachments, marked in green, become unstable (on the right) compared to normal (on the left).
Credit: Cook and Salmon labs, UNC School of Medicine

The foundation of biological inheritance is DNA replication -- a tightly coordinated process in which DNA is simultaneously copied at hundreds of thousands of different sites across the genome. If that copying mechanism doesn't work as it should, the result could be cells with missing or extra genetic material, a hallmark of the genomic instability seen in most birth defects and cancers.

Related Articles


University of North Carolina School of Medicine scientists have discovered that a protein known as Cdt1, which is required for DNA replication, also plays an important role in a later step of the cell cycle, mitosis. The finding presents a possible explanation for why so many cancers possess not just genomic instability, but also more or less than the usual 46 DNA-containing chromosomes.

The new research, which was published online ahead of print by the journal Nature Cell Biology, is the first to definitively show such a dual role for a DNA replication protein.

"It was such a surprise, because we thought we knew what this protein's job was -- to load proteins onto the DNA in preparation for replication," said Jean Cook, PhD, associate professor of biochemistry and biophysics and pharmacology at the UNC School of Medicine and senior study author. "We had no idea it also had a night job, in a completely separate part of the cell cycle."

The cell cycle is the series of events that take place in a cell leading to its growth, replication and division into two daughter cells. It consists of four distinct phases: G1 (Gap 1), S (DNA synthesis), M (mitosis) and G2 (Gap 2). Cook's research focuses on G1, when Cdt1 places proteins onto the genetic material to get it ready to be copied.

In this study, Cook ran a molecular screen to identify other proteins that Cdt1 might be interacting with inside the cell. She expected to just find more entities that controlled replication, and was surprised to discover one that was involved in mitosis. That protein, called Hec1 for "highly expressed in cancer," helps to ensure that the duplicated chromosomes are equally divided into daughter cells during mitosis, or cell division. Cook hypothesized that either Hec1 had a job in DNA replication that nobody knew about, or that Cdt1 was the one with the side business.

Cook partnered with Hec1 expert Edward (Ted) D. Salmon, PhD, professor of biology and co-senior author in this study, to explore these two possibilities. After letting Cdt1 do its replication job, the researchers interfered with the protein's function to see if it adversely affected mitosis. Using a high-powered microscope that records images of live cells, they showed that cells where Cdt1 function had been blocked did not undergo mitosis properly.

Once the researchers knew that Cdt1 was involved in mitosis, they wanted to pinpoint its role in that critical process. They further combined their genetic, microscopy and computational methods to demonstrate that without Cdt1, Hec1 fails to adopt the conformation inside the cells necessary to connect the chromosomes with the structure that pulls them apart into their separate daughter cells.

Cook says cells that make aberrant amounts of Cdt1, like that seen in cancer, can therefore experience problems in both replication and mitosis. One current clinical trial is actually trying to ramp up the amount of Cdt1 in cancer cells, in the hopes of pushing them from an already precarious position into a fatal one.

The research was funded by the National Institutes of Health. Study co-authors from UNC were Dileep Varma; Srikripa Chandrasekaran; Karen T. Reidy; and Xiaohu Wan.


Story Source:

The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Dileep Varma, Srikripa Chandrasekaran, Lynsie J. R. Sundin, Karen T. Reidy, Xiaohu Wan, Dawn A. D. Chasse, Kathleen R. Nevis, Jennifer G. DeLuca, E. D. Salmon, Jeanette Gowen Cook. Recruitment of the human Cdt1 replication licensing protein by the loop domain of Hec1 is required for stable kinetochore–microtubule attachment. Nature Cell Biology, 2012; DOI: 10.1038/ncb2489

Cite This Page:

University of North Carolina School of Medicine. "DNA replication protein also has a role in mitosis, cancer." ScienceDaily. ScienceDaily, 13 May 2012. <www.sciencedaily.com/releases/2012/05/120513144630.htm>.
University of North Carolina School of Medicine. (2012, May 13). DNA replication protein also has a role in mitosis, cancer. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2012/05/120513144630.htm
University of North Carolina School of Medicine. "DNA replication protein also has a role in mitosis, cancer." ScienceDaily. www.sciencedaily.com/releases/2012/05/120513144630.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Sunday, December 21, 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
Monarch Butterflies Descend Upon Mexican Forest During Annual Migration

Monarch Butterflies Descend Upon Mexican Forest During Annual Migration

Reuters - Light News Video Online (Dec. 19, 2014) Millions of monarch butterflies begin to descend onto Mexico as part of their annual migration south. Rough Cut (no reporter narration) Video provided by Reuters
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
Powered by NewsLook.com
Birds Might Be Better Meteorologists Than Us

Birds Might Be Better Meteorologists Than Us

Newsy (Dec. 19, 2014) A new study suggests a certain type of bird was able to sense a tornado outbreak that moved through the U.S. a day before it hit. 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