Navigation Links
At the crossroads of chromosomes

PHILADELPHIA On average, one hundred billion cells in the human body divide over the course of a day. Most of the time the body gets it right but sometimes, problems in cell replication can lead to abnormalities in chromosomes resulting in many types of disorders, from cancer to Down Syndrome.

Now, researchers at the University of Pennsylvania's School of Medicine have defined the structure of a key molecule that plays a central role in how DNA is duplicated and then moved correctly and equally into two daughter cells to produce two exact copies of the mother cell. Without this molecule, entire chromosomes could be lost during cell division.

Ben Black, PhD, assistant professor of Biochemistry and Biophysics, and Nikolina Sekulic, PhD, a postdoctoral fellow in the Black lab, report in the September 16 issue of Nature the structure of the CENP-A molecule, which defines a part of the chromosome called the centromere. This is a constricted area to which specialized molecules called spindle fibers attach that help pull daughter cells apart during cell division.

"Our work gives us the first high-resolution view of the molecules that control genetic inheritance at cell division," says Black. "This is a big step forward in a puzzle that biologists have been chipping away at for over 150 years."

Investigators have known for the last 15 years that part of cell division is controlled by epigenetic processes, the series of actions that affect the protein spools around which DNA is tightly bound, rather than encoded in the DNA sequence itself. Those spools are built of histone proteins, and chemical changes to these spool proteins can either loosen or tighten their interaction with DNA. Epigenetics alter the readout of the genetic code, in some cases ramping a gene's expression up or down. In the case of the centromere, it marks the site where spindle fibers attach independently of the underlying DNA sequence. CENP-A has been suspected to be the key epigenetic marker protein.

However, what hasn't been known is how CENP-A epigenetically marks the centromere to direct inheritance. The Black team found the structural features that confer CENP-A the ability to mark centromere location on each chromosome. This is important because without CENP-A or the centromere mark it creates, the entire chromosomeand all of the genes it housesare lost at cell division.

In this study, Black solved CENP-A's structure to determine how it specifically marks the centromere on each chromosome and surmise from that how the epigenetic mark is copied correctly in each cell division. They found that CENP-A changes the shape of the nucleosome of which it's a part, also making it more rigid than other nucleosomes without CENP-A. The nucleosome is the combination of DNA wound around a histone protein core --the DNA thread wrapped around the histone spool. The CENP-A nucleosome is copied several times to create a unique epigenetic area, different from the rest of the chromosome. CENP-A replaces histone H3 in the nucleosomes located at the centromere.

This CENP-A centromere identifier attracts other proteins, and in cell division builds a massive structure, the kinetochore, for pulling the duplicated chromosomes apart during cell division.

Besides the major advance in the understanding of the molecules driving human inheritance, this work also brings about the exciting prospect that the key epigenetic components are now in hand to engineer clinically useful artificial chromosomes that will be inherited alongside our own natural chromosomesand with the same high fidelity, says Black.


Contact: Karen Kreeger
University of Pennsylvania School of Medicine

Related biology news :

1. Colorado State University biochemists study how chromosomes unravel to let genes do their jobs
2. Tumor suppressor p53 prevents cancer progression in cells with missegregated chromosomes
3. Longevity tied to genes that preserve tips of chromosomes
4. Genetic conflict in fish led to evolution of new sex chromosomes
5. UGA researchers propose model for disorders caused by improper transmission of chromosomes
6. Female human embryos adjust the balance of X chromosomes before implantation
7. Slicing chromosomes leads to new insights into cell division
8. Evolutionary origin of bacterial chromosomes revealed
9. How chromosomes meet in the dark -- Switch that turns on X chromosome matchmaking
10. Keeping chromosomes from cuddling up
Post Your Comments:
Related Image:
At the crossroads of chromosomes
(Date:4/15/2016)... April 15, 2016  A new partnership announced ... accurate underwriting decisions in a fraction of the ... priced and high-value life insurance policies to consumers ... With Force Diagnostics, rapid testing (A1C, Cotinine ... readings (blood pressure, weight, pulse, BMI, and activity ...
(Date:3/31/2016)... , March 31, 2016   ... ("LegacyXChange" or the "Company") LegacyXChange is excited ... of its soon to be launched online site for ... ) will also provide potential shareholders a ... DNA technology to an industry that is notorious for ...
(Date:3/22/2016)... 22, 2016 According ... Market for Consumer Industry by Type (Image, Motion, ... (Communication & IT, Entertainment, Home Appliances, & ... to 2022", published by MarketsandMarkets, the market ... reach USD 26.76 Billion by 2022, at ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... 2016 , ... Charm Sciences, Inc. is pleased to announce ... Research Institute approval 061601. , “This is another AOAC-RI approval of the Peel ... President of Regulatory and Industrial Affairs. “The Peel Plate methods perform comparably to ...
(Date:6/23/2016)... -- The Biodesign Challenge (BDC), a university competition that asks ... systems and biotechnology, announced its winning teams at the ... York City . The teams, chosen ... MoMA,s Celeste Bartos Theater during the daylong summit. Keynote ... of architecture and design, and Suzanne Lee , ...
(Date:6/23/2016)... ... June 23, 2016 , ... Supplyframe, ... of the Supplyframe Design Lab . Located in Pasadena, Calif., the Design ... of how hardware projects are designed, built and brought to market. , The ...
(Date:6/23/2016)... Durham, NC (PRWEB) , ... June 23, 2016 , ... ... Odense University Hospital in Denmark detail how a patient who developed lymphedema after being ... (fat) tissue. The results could change the paradigm for dealing with this debilitating, frequent ...
Breaking Biology Technology: