Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


LICR/UCSD team solves mystery of centromeres


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:

More articles from Life Sciences:

nachricht Bioluminescent sensor causes brain cells to glow in the dark
28.10.2016 | Vanderbilt University

nachricht Activation of 2 genes linked to development of atherosclerosis
28.10.2016 | Brigham and Women's Hospital

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel light sources made of 2D materials

Physicists from the University of Würzburg have designed a light source that emits photon pairs. Two-photon sources are particularly well suited for tap-proof data encryption. The experiment's key ingredients: a semiconductor crystal and some sticky tape.

So-called monolayers are at the heart of the research activities. These "super materials" (as the prestigious science magazine "Nature" puts it) have been...

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Steering a fusion plasma toward stability

28.10.2016 | Power and Electrical Engineering

Bioluminescent sensor causes brain cells to glow in the dark

28.10.2016 | Life Sciences

Activation of 2 genes linked to development of atherosclerosis

28.10.2016 | Life Sciences

More VideoLinks >>>