Scientists discover how key proteins segregate vital genetic information during mitosis

August 6, 2015, The Wistar Institute
Human chromosomes during metaphase. Credit: Steffen Dietzel/Wikipedia

Chromosomes are responsible for carrying our genes and essentially protecting the information that helps ensure normal, healthy growth, with vital instructions being passed on from cell to cell by a process known as mitosis. While this copying mechanism has been well understood for decades, scientists have been unable to describe exactly how genetic information is protected and properly segregated as mitosis is happening.

Now, new research from The Wistar Institute has identified an interaction between proteins that provides a pivotal role in organizing chromosomes so that vital genetic information gets passed on safely.

The results of the study were published online by the journal Molecular Cell.

To understand how dividing cells protect and faithfully segregate genes that have been transcribed, researchers focused on a protein complex found in human cells called condensin. This set of proteins helps compact more than 20,000 protein-coding genes in the human genome into something that can fit inside the nucleus of each of our cells. Recent studies have found that condensin genes are heavily mutated in various cancers. These mutations promote cancer-causing processes through dysregulation of as well as chromosomal instability.

Ken-ichi Noma, Ph.D., associate professor in Wistar's Gene Expression and Regulation program, studies how disorganization of a cell's nucleus can lead to cancer. Identifying the relationships between proteins that are responsible for protecting chromosomes is a crucial step in learning more about some of the first disruptions of our genes that result in disease.

"How condensin is able to assemble the specific structure of mitotic chromosomes and how this organization promotes segregation during are two significant questions that have faced those of us working in genome biology," Noma said. "We believe this study provides a molecular basis for these important questions."

Previously, Noma's lab showed that many genes are connected to centromeres. Centromeres are sites where two chromatids - copies of newly replicated chromosomes - are positioned to be properly split up during mitosis. Condensin mediates the clustering of RNA polymerase III-transcribed genes (abbreviated Pol III genes) and Pol II-transcribed "housekeeping" genes that are necessary for every cell to function properly. However, scientists did not know exactly how the condensin was being recruited to aid in this process.

In this study, Noma and his colleagues identified the interactions of proteins that link condensin and mitosis. By studying mitosis in yeast, they were able to identify a subunit of condensin called Cnd2 that binds directly to a protein called the TATA box-binding protein (TBP). TBP is a general transcription factor required for every type of transcription. When Cnd2 binds to TBP, it recruits condensin onto Pol III genes and Pol II-transcribed housekeeping genes. When this happens, condensin tethers these to the centromeres so that when mitosis occurs, the remains protected and intact as the chromatins are split apart.

"This genome-organizing mechanism contributes to effective transmission of important genetic materials during mitosis," Noma said. "By gaining a better understanding of this essential process, we can now study the origins of diseases that arise when this phenomenon is disrupted."

"This is a very elegant example of how Wistar science can broaden our understanding of basic mechanisms of important biologic processes, in this particular case, chromosomal segregation during cell division," said Dario C. Altieri, M.D., president and CEO of The Wistar Institute and director of The Wistar Institute's Cancer Center. "The information obtained from this type of work is pivotal for a better understanding of human diseases and potential new therapies."

Explore further: 'Master controller' behind DNA structure reorganization during senescence identified

Related Stories

How to make chromosomes from DNA

July 28, 2015

Researchers at the University of Tokyo have discovered a long-overlooked process important for converting a long, string-like DNA molecule into a chromosome. This finding gives us a better understanding of the mechanism of ...

Protein scaffold

May 27, 2015

Right before a cell starts to divide to give birth to a daughter cell, its biochemical machinery unwinds the chromosomes and copies the millions of protein sequences comprising the cell's DNA, which is packaged along the ...

New key mechanism in cell division discovered

May 18, 2012

Researchers from the Bellvitge Biomedical Research Institute (IDIBELL) have identified the mechanism by which protein Zds1 regulates a key function in mitosis, the process that occurs immediately before cell division. The ...

Recommended for you

Paleontologists report world's biggest Tyrannosaurus rex

March 22, 2019

University of Alberta paleontologists have just reported the world's biggest Tyrannosaurus rex and the largest dinosaur skeleton ever found in Canada. The 13-metre-long T. rex, nicknamed "Scotty," lived in prehistoric Saskatchewan ...

NASA instruments image fireball over Bering Sea

March 22, 2019

On Dec. 18, 2018, a large "fireball—the term used for exceptionally bright meteors that are visible over a wide area—exploded about 16 miles (26 kilometers) above the Bering Sea. The explosion unleashed an estimated 173 ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.