Navigation Links
DNA replication protein also has a role in mitosis, cancer
Date:5/13/2012

CHAPEL HILL, N.C. 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.

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.


'/>"/>

Contact: Les Lang
llang@med.unc.edu
919-966-9366
University of North Carolina School of Medicine
Source:Eurekalert  

Related biology news :

1. JDRF-funded researchers discover proteins regulating human beta cell replication
2. Visualizing virus replication in three dimensions
3. New strategy for inhibiting virus replication
4. CSHL scientists uncover role of protein critical for activating DNA replication
5. Retrovirus replication process different than thought
6. Chimerix Antiviral CMX001 Inhibits JC Virus Replication in Preclinical Study; Late-Breaker Presented at Antiviral Congress 2010
7. Collisions of protein machines cause DNA replication derailment
8. Research into chromosome replication reveals details of heredity dynamics
9. In vitro infection and replication of hepatitis E virus in human hepatocytes
10. UBC megapixel DNA replication technology promises faster, more precise diagnostics
11. Study reveals new role for RNA interference during chromosomal replication
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
DNA replication protein also has a role in mitosis, cancer
(Date:2/13/2017)... 13, 2017  RSA Conference -- RSA, a Dell ... designed to enhance fraud detection and investigation across ... RSA Fraud & Risk Intelligence Suite. The new ... additional insights from internal and external sources as ... their customers from targeted cybercrime attacks. ...
(Date:2/8/2017)... Feb. 7, 2017  Aware, Inc. (NASDAQ: AWRE ... reported financial results for its quarter and year ended December ... of 2016 was $3.9 million compared to $6.9 million in ... quarter of 2016 was $0.6 million compared to $2.6 million ... fourth quarter of 2016 was $0.5 million, or $0.02 per ...
(Date:2/7/2017)... 2017 Zimmer Biomet Holdings, Inc. (NYSE and ... present at the LEERINK Partners 6th Annual Global Healthcare ... Wednesday, February 15, 2017 at 10 a.m. Eastern Time. ... can be accessed at http://wsw.com/webcast/leerink28/zbh .  The webcast ... Zimmer Biomet,s Investor Relations website at http://investor.zimmerbiomet.com . ...
Breaking Biology News(10 mins):
(Date:2/24/2017)... , Feb. 24, 2017  OncoSec Medical Incorporated ("OncoSec") ... will host a Key Opinion Leader event to highlight ... oral and poster presentation at the upcoming 2017 ASCO-SITC ... KOL event will be held in-person and via live ... / 9:00 AM PST at the Lotte New York ...
(Date:2/23/2017)... Feb. 23, 2017  MIODx announced today that ... key immunotherapy technologies from the University of California, ... method to monitor a patient for response to ... CTLA-4.  The second license extends the technology with ... likely to have an immune-related adverse event (IRAE) ...
(Date:2/23/2017)... ... February 23, 2017 , ... Baltimore ... multiple immunoassay-based threat detection technologies by researchers from the Pacific National Northwest ... detection technology was found to have the best level of detection (LOD) ...
(Date:2/23/2017)... , Feb. 23, 2017 Aviva ... tools, announced the acquisition of GenWay Biotech Incorporated, ... comprehensive service and product offering for both the ... will facilitate growth and enhance capabilities for both ... and ELISA assays will nicely complement ASB,s objective ...
Breaking Biology Technology: