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:11/17/2015)... 2015  Vigilant Solutions announces today that Mr. ... Directors. --> --> ... the partnership at TPG Capital, one of the largest ... Billion in revenue.  He founded and led TPG,s Operating ... companies, from 1997 to 2013.  In his first role, ...
(Date:11/16/2015)... Nov 16, 2015  Synaptics Inc. (NASDAQ: ... solutions, today announced expansion of its TDDI product ... touch controller and display driver integration (TDDI) solutions ... These new TDDI products add to the previously-announced ... TD4302 (WQHD resolution), and TD4322 (FHD resolution) solutions. ...
(Date:11/12/2015)... Mass. , Nov. 12, 2015  Arxspan ... Institute of MIT and Harvard for use of ... discovery information management tools. The partnership will support ... both biological and chemical research information internally and ... will be used for managing the Institute,s electronic ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... PHILADELPIA, PA (PRWEB) , ... November 24, 2015 , ... ... young entrepreneurs at competitive events in five states to develop and pitch their BIG ... student projects from each state are competing for votes to win the title of ...
(Date:11/24/2015)... , Nov. 24, 2015 /PRNewswire/ - Aeterna Zentaris ... today that the remaining 11,000 post-share consolidation (or ... Warrants (the "Series B Warrants") subject to the ... on November 23, 2015, which will result in ... giving effect to the issuance of such shares, ...
(Date:11/24/2015)... Telbec/ - ProMetic Life Sciences Inc. (TSX: PLI) (OTCQX: PFSCF) ... Laurin , President and Chief Executive Officer of ProMetic, will ... 27 th Annual Healthcare Conference to be held at ... st , at 8.50am (ET) and ProMetic,s management ... The presentation will be available live via a webcast accessible ...
(Date:11/24/2015)... (PRWEB) , ... November 24, 2015 , ... Whitehouse Laboratories ... Laboratory. The new stand-alone facility will be strictly dedicated to basic USP 61, ... and existing clients the chance to have complete chemistry and micro testing performed by ...
Breaking Biology Technology: