Featured Research

from universities, journals, and other organizations

Single Missing Protein May Result In Down Syndrome And Other Human Chromosomal Birth Defects

Date:
September 17, 2009
Source:
Florida State University
Summary:
Using yeast genetics and a novel scheme to selectively remove a single protein from the cell division process called meiosis, a cell biologist found that when a key molecular player known as Pds5 goes missing, chromosomes fail to segregate and pair up properly, and birth defects such as Down syndrome can result.

Looking at the yeast genome: this is the genetic material of this organism.
Credit: Hong-Guo Yu/FSU Dept. of Biological Science

Using yeast genetics and a novel scheme to selectively remove a single protein from the cell division process called meiosis, a cell biologist at The Florida State University found that when a key molecular player known as Pds5 goes missing, chromosomes fail to segregate and pair up properly, and birth defects such as Down syndrome can result.

Related Articles


That discovery is groundbreaking, but so, too, is what principal investigator Hong-Guo Yu calls the "genetics trick" performed by his research team that made the discovery possible. The study shines new light on the protein Pds5, its crucial regulatory role during meiosis, and the impact of its absence on the molecular-level genesis of human chromosomal birth defects that include Down, Edwards, Patau, Turner, Klinefelter's and XYY syndromes.

The findings, which are described in a paper featured in the Journal of Cell Biology, may contribute to the eventual development of targeted, molecular-level interventions.

Yu, an assistant professor in FSU's Department of Biological Science, explained how the meiotic stage is set and what goes wrong when key elements are rearranged.

"To produce a genetically balanced gamete (sperm and egg), the cell must contend with two sets of chromosome pairs, homologs and sisters," he said. "Homologs are the nearly identical chromosomes inherited from each parent; sisters are exactly identical pairs that are produced like photocopies as part of normal cell division.

"During normal meiosis, the process of division that halves the number of chromosomes per cell, my colleagues and I discovered that Pds5 regulates the pairing and synapsis (joining together) of 'mom and dad' homologs. We also learned that Pds5 plays a vital role in the synaptonemal complex, a glue-like protein structure that homologs use to literally stick together as they pair up. In addition, we found that, although sister chromatids enter meiosis in very close proximity to one another, Pds5 acts to inhibit synapsis between them, a good thing because, then, meiotic conditions support the necessary pairing of homologs."

Consequently, removing Pds5 during meiosis triggers a chromosomal catastrophe.

"In order to observe what happened when the Pds5 went missing from the process, we performed a 'molecular genetics trick' that had never been applied to this particular protein before, and it worked," Yu said. "We successfully engineered yeast cells that shut down Pds5 only during meiosis, but not when they were vegetative."

As a result, Pds5 was no longer present to regulate homolog organization and transmission in the meiotic yeast cells. The synaptonemal complex, which normally would support the synapsis of homologs by creating a sticky bond along their entire length, failed to form. In the meiotic malfunction that followed, the identical sister chromosomes began to synapse instead.

"When Pds5 is removed and sister chromatids become synapsed as a result, the segregation and recombination of homologs essential for genetic diversity fails," Yu said. "This finding is highly important, because failure to generate a crossover between homologs leads to chromosome missegregation and can cause human chromosomal birth defects such as Down syndrome, which affects about one in 800 newborns in the United States."

Yu said the landmark study has significantly extended previous observations of the role of Pds5 in the formation of meiotic chromosome structure.

"Now, we are investigating the other factors that interact with Pds5 during meiosis to regulate chromosome segregation and homolog synapsis," he said. "Long term, we hope to achieve a comprehensive understanding of the molecular mechanisms behind chromosomal birth defects and see our research contribute to the creation of targeted interventions during meiosis."

Currently, Yu's research at Florida State University is supported by a two-year, $150,000 Basil O'Connor Starter Scholar award from the March of Dimes Foundation, and by a three-year, $375,000 Bankhead Coley grant from the Florida Biomedical Research Program.


Story Source:

The above story is based on materials provided by Florida State University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Jin et al. Pds5 is required for homologue pairing and inhibits synapsis of sister chromatids during yeast meiosis. The Journal of Cell Biology, 2009; 186 (5): 713 DOI: 10.1083/jcb.200810107

Cite This Page:

Florida State University. "Single Missing Protein May Result In Down Syndrome And Other Human Chromosomal Birth Defects." ScienceDaily. ScienceDaily, 17 September 2009. <www.sciencedaily.com/releases/2009/09/090916153147.htm>.
Florida State University. (2009, September 17). Single Missing Protein May Result In Down Syndrome And Other Human Chromosomal Birth Defects. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2009/09/090916153147.htm
Florida State University. "Single Missing Protein May Result In Down Syndrome And Other Human Chromosomal Birth Defects." ScienceDaily. www.sciencedaily.com/releases/2009/09/090916153147.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins