Stem cells: Tuning the death sentence

Jan 23, 2013

In this week's issue of Science Signaling (22 January, 2013), Danen and colleagues of the Division of Toxicology of LACDR report novel insights into the question how stem cells decide to commit suicide when their DNA is damaged.

It is known that damaged DNA, especially in stem cells can lead to accumulation of potentially dangerous mutations that may be a source for cancer. To prevent this, evolution has provided our cells with the ability to recognize damaged DNA and to rapidly respond to it. This so-called "" activates repair mechanisms, and, if damage is too severe to repair, turns on a cascade of events leading to .

All cells in our body are constantly experiencing small injuries in their DNA, for instance due to UV light or chemicals. It is important that cells first try to repair damaged DNA and only decide to commit suicide if damage is beyond repair. If suicide signals would be turned on too fast, in our tissues might be depleted causing premature aging. The discovery published in this week's Science Signaling is a new mechanism that acts as a break on the suicide signals.

In collaboration with colleagues from the Department of Toxicogenetics of the LUMC and from the University of Copenhagen, Danen et al. have been able to integrate several large-scale analyses to unravel the events that make up the DNA damage response. Genome-wide changes in and protein modifications, as well as genome-wide "gene silencing" screens were integrated with bioinformatics tools to create signaling networks. This was possible through extensive collaboration within the NGI-funded, "Netherlands Toxicogenomics Center".

The signaling networks point to novel methods to recognize chemicals or drugs that activate a DNA damage response and hence, might be dangerous for . At the same time, the networks provide new clues for why are often able to avoid activation of suicide signals when exposed to radiotherapy or chemotherapy. The publication in Science Signaling is one of the outcomes of this project; additional publications will come out this year.

Explore further: Mycologist promotes agarikon as a possibility to counter growing antibiotic resistance

add to favorites email to friend print save as pdf

Related Stories

Refusal of suicide order: Why tumor cells become resistant

Jun 23, 2008

Cells with irreparable DNA damage normally induce programmed cell death, or apoptosis. However, this mechanism often fails in tumor cells so that transformed cells are able to multiply and spread throughout the body. Scientists ...

Recommended for you

YEATS protein potential therapeutic target for cancer

Oct 23, 2014

Federal Express and UPS are no match for the human body when it comes to distribution. There exists in cancer biology an impressive packaging and delivery system that influences whether your body will develop cancer or not.

Precise and programmable biological circuits

Oct 23, 2014

A team led by ETH professor Yaakov Benenson has developed several new components for biological circuits. These components are key building blocks for constructing precisely functioning and programmable bio-computers.

User comments : 0