Enzyme controls transport of genomic building blocks

Mar 06, 2014
This is Ilnaz Klimovskaia in the lab. Credit: Anja Groth, BRIC

Our DNA and its architecture are duplicated every time our cells divide. Histone proteins are key building blocks of this architecture and contain crucial information that regulates our genes. Danish researchers show how an enzyme controls reliable and high-speed delivery of histones to DNA copying hubs in our cells. This shuttling mechanism is crucial to maintain normal function of our genes and prevent disease.

The results are published in the journal Nature Communications.

Interdisciplinary research team finds cellular high-speed shuttle

An interdisciplinary team of researchers from BRIC, University of Copenhagen and University of Southern Denmark have identified a cellular transport mechanism so fast and finely tuned that it compares to an Asian fast-speed train.

"Using advanced laboratory techniques, we have revealed how an enzyme called TLK1 regulates the transport of to DNA copying hubs in our . Such a devoted supply of histones, is crucial to maintain the genomic architecture when our cells divide", says Ilnaz Klimovskaia who has been spearheading the experimental work as part of her PhD-studies at BRIC.

The new results show that TLK1 controls the activity of a molecule called Asf1. Asf1 act as a freight train that transports histones to the nuclei of our cells where the DNA is copied during cell divisions. The enzymatic activity of TLK1 turn Asf1 into a fast-speed train, capable of precise, fast and timely transport of histones to newly formed DNA.

TLK1 contribute to cellular identity

Histones play an important role for the activity of our , as they contain information that can turn on or off genes. The information is communicated only when DNA is wrapped around the histones, to form the ordered genomic architecture called chromatin. As all our cells contain exactly the same genes, the histone information is crucial to activate only the sub-set of genes necessary to maintain a certain cellular identity. For example, heart genes needs only to be turned on in heart cells, but turned off in other cell types.

"We show that TLK can boost the supply of histones at critical time points. By controlling the transport of histones to our DNA, TLK and Asf1 ensure that the chromatin architecture and its information are copied correctly during cell division, so that cell identity is maintained", explains Ilnaz Klimovskaia.

Loss of chromatin integrity in cancer development

A tight coordination between DNA duplication and supply of major chromatin like histones, are crucial to maintain normal function of our cells. If the chromatin architecture is wrong, it can affect both gene expression as well as the stability of our DNA. Together, this is a dangerous cocktail that might fuel cellular changes and lead to .

"Our research adds a new layer to the understanding of how chromatin is maintained when cells in our body divides. This information is crucial to understand how cells maintain their identity and protect their genome, which is essential to avoid cancer development", says associate professor Anja Groth, who has been heading the research team.

The next step for the research team is to dig deeper into the understanding of how duplication is controlled. The team is also exploring whether targeting of the TLK enzyme could be useful in cancer therapy, as they speculate that reducing the supply of histones in highly dividing cancer cells, might make tumor cells more vulnerable to already existing cancer drugs.

Explore further: New technology detect cellular memory

add to favorites email to friend print save as pdf

Related Stories

New technology detect cellular memory

Feb 24, 2014

Cells in our body are constantly dividing to maintain our body functions. At each division, our DNA code and a whole machinery of supporting components has to be faithfully duplicated to maintain the cell's ...

Defect in transport system causes DNA chaos in red blood cells

Mar 12, 2012

Within all our cells lies two meters of DNA, highly ordered in a structure of less than 10 micro meters in diameter. Special proteins called histones act as small building bricks, organising our DNA in this structure. Preservation ...

Researchers discover new mechanism of gene regulation

Feb 26, 2014

In the cells of humans and other organisms, only a subset of genes are active at any given time, depending largely on the stage of life and the particular duties of the cell. Cells use different molecular mechanisms to orchestrate ...

New mechanism for genome unpacking in stem cells

Jan 27, 2014

Scientists at Karolinska Institutet and Gurdon Institute in Cambridge, United Kingdom have identified a novel mechanism that allows pluripotent stem cells to maintain their genome in an unpacked state, and thereby maintain ...

Recommended for you

Environmental pollutants make worms susceptible to cold

Sep 19, 2014

Some pollutants are more harmful in a cold climate than in a hot, because they affect the temperature sensitivity of certain organisms. Now researchers from Danish universities have demonstrated how this ...

Interactions of Earth's smallest players have global impact

Sep 19, 2014

A new study reveals the interactions among bacteria and viruses that prey on them thriving in oxygen minimum zones—stretches of ocean starved for oxygen that occur around the globe. Understanding such microbial ...

A new quality control pathway in the cell

Sep 18, 2014

Proteins are important building blocks in our cells and each cell contains millions of different protein molecules. They are involved in everything from structural to regulatory aspects in the cell. Proteins are constructed ...

User comments : 0