Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

LICR/UCSD team solves mystery of centromeres

29.07.2004


The genetic machinery for proper cell division



Researchers at the Ludwig Institute for Cancer Research at the University of California, San Diego (UCSD) School of Medicine have solved one of genetics’ mysteries – how a segment of protein on each of the body’s DNA-carrying chromosomes is able to form a rigid structure called a centromere, leading to proper cell division and the faithful inheritance of genes.

Published in the July 29, 2004 issue of the journal Nature, the study utilized a sophisticated new form of mass spectrometry developed at the UCSD School of Medicine to determine how a protein called CENP-A, turns the normally flexible center section of a rod-shaped chromosome into a steel-like structure called a centromere.


A crucial player in the complicated process of cell division, the centromere is responsible for moving the correct number of chromosomes into a new cell. Learning how a centromere forms is an important step in understanding what goes wrong in cell division. When either too many or too few chromosomes end up in newly formed cells, the catastrophic result is often birth defects, spontaneous abortion, or cancer. For example, Down syndrome is a disorder caused by one too many copies of chromosome 21.

During cell division, each cell makes a duplicate copy of its chromosomes. Each pair of identical chromosomes forms a centromere that holds them together in the center, like a cinched waist in an "X". From opposite poles of the cell, microtubules called spindle fibers, extend down to the centromeres and act as ropes to pull the centromere and paired chromosome apart, so that half the centromere/chromosome moves to one side of the cell, while the other half goes to the opposite pole. Cell division follows, resulting in two identical daughter cells.

"Ever since Mendel’s original genetic studies, we’ve wondered how it is that centromeres function to assure that chromosomes are faithfully inherited," said the study’s senior author, Don Cleveland, Ph.D., UCSD professor of medicine, neurosciences and cellular and molecular medicine, as well as a member of the Ludwig Institute for Cancer Research.

While many genes have similar DNA sequences in all organisms (yeast, flies, worms, mice, humans, etc.), researchers have determined that the DNA in centromeres varies markedly from species to species.

"It has been perplexing," Cleveland said. "Although the DNA sequence doesn’t matter, we’ve been able to show that a particular protein, CENP-A, determines where the centromere is located and copies this same location to a newly synthesized chromosome. The presence of CENP-A turns the centromere into a staff DNA and protein complex, and ensures that the centromere is maintained every time a cell duplicates. This is a critical component of the cellular machinery that provides every person on earth with a nearly identical set of chromosomes."

In the UCSD investigation, researchers made purified, synthetic copies of human CENP-A protein, which they studied in the laboratory. CENP-A, which binds only to centromeres, is a variation of the more common histone 3 (H3), a protein located throughout all regions of chromosomes.

The study’s first author, Ben E. Black, Ph.D., a post-doctoral fellow in Cleveland’s laboratory, was able to characterize the function of CENP-A with a UCSD School of Medicine invention called enhanced amide hydrogen/deuterium-exchange mass spectrometry, or DXMS*. This methodology, developed by Virgil L. Woods, Jr., M.D., associate professor of medicine and one of the paper’s corresponding authors, enables rapid analysis of protein structure and motion (dynamics) at the molecular level.

Black performed DXMS analysis of CENP-A in the Woods’ lab and identified a region of the protein that was much more rigid than similar regions of H3. He then genetically "transplanted" this small, stiff region of CENP-A into H3, and found that the "stiffened-up" H3 acted just like CENP-A, binding to centromeres.

"With DXMS, we were able to find the small region within CENP-A responsible for its ability to locate and then rigidify the centromere," Black said.

Cleveland added that "biologists have been able to take what are, in essence, snapshots of the structure of proteins for many years, but you couldn’t see whether regions of the protein were rigid or flexible. Now, with DXMS, we’re able to see something more like a movie that shows how flexible the regions of a protein are."

Woods noted that "this work demonstrates the ability of DXMS to precisely localize proteinfeatures responsible for function, even when the function is a very complex one – in this case, the initiation of centromere formation."

Sue Pondrom | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Superconducting vortices quantize ordinary metal

Russian researchers together with their French colleagues discovered that a genuine feature of superconductors -- quantum Abrikosov vortices of supercurrent -- can also exist in an ordinary nonsuperconducting metal put into contact with a superconductor. The observation of these vortices provides direct evidence of induced quantum coherence. The pioneering experimental observation was supported by a first-ever numerical model that describes the induced vortices in finer detail.

These fundamental results, published in the journal Nature Communications, enable a better understanding and description of the processes occurring at the...

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Rapid water formation in diffuse interstellar clouds

25.06.2018 | Physics and Astronomy

Using tree-fall patterns to calculate tornado wind speed

25.06.2018 | Earth Sciences

'Stealth' material hides hot objects from infrared eyes

25.06.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>