New light shed on chromosome fragility

Dec 26, 2011

Why are certain chromosome regions prone to breakages? The answer is crucial, as this fragility is involved in the development of tumors. A team from the Institut de Génétique et de Biologie Moleculaire et Cellulaire (CNRS, France) has partially lifted the veil on the mystery. Laszlo Tora and his colleagues have discovered that breakages in the longest human genes are due to a phenomenon previously considered improbable in mammalian cells: an interference between two key gene processes, DNA transcription and replication. Published in the review Molecular Cell of 23 December 2011, this work could give rise to novel anti-tumor strategies in the longer term.

Tora and his colleagues began by studying the transcription of very large human genes (over 800 kilobases), known to exhibit DNA breaks called “common fragile sites”. They hypothesized that, since the time required for the transcription of these very large genes is extremely long, the transcription process could be involved in the appearance of fragile sites.

To test their hypothesis, the researchers used the flow cytometry technique, which enabled them to sort the cells according to their progression through the cell cycle - cells in the G1 (gene transcription and cell growth), S (DNA replication), G2 (growth and preparation for cell division) and M (cell division) phases. It appears that the transcription of very large genes far exceeds the duration of the cell cycle, and is only completed in the early stages of the following cycle, in the G1 or S phase. This comes as a surprise since gene transcription in mammals was thought to occur within a single and mainly in the G1 phase.

Since replication takes place in the S phase, the researchers suspected interference between transcription and replication to explain the breakages in very large mammalian genes. They studied the replication process in these and found out that replication in the fragile site region takes place at the end of the S phase, while transcription is still ongoing in the same regions! This discovery revolutionizes current genetic knowledge, as it was generally admitted that DNA transcription and replication in mammals could not take place at the same time.

The team went further and sought to elucidate what could weaken DNA when and transcription happen simultaneously. They highlighted lasting loop structures, caused by the hybridization of DNA with the RNA molecule produced during . These DNA/RNA loops could destabilize DNA and cause breakages in the event of stress.

This major discovery opens new perspectives in terms of medical research: the famous loops appear as potential targets for reducing genomic instability and the onset of tumors.

Explore further: Fighting bacteria—with viruses

add to favorites email to friend print save as pdf

Related Stories

Dundee researchers make gene breakthrough

Sep 16, 2011

Researchers at the University of Dundee have made a significant breakthrough in understanding how human cells decode genes important for cell growth and multiplication.

Scientists identify molecular basis for DNA breakage

Jul 19, 2011

Scientists from the Hebrew University have identified the molecular basis for DNA breakage, a hallmark of cancer cells. The findings of this research have just been published in the journal Molecular Cell.

Scripps research team unravels new cellular repair mechanism

Aug 06, 2008

A Scripps Research team has unraveled a new biochemical pathway that triggers a critical repair response to correct errors in the DNA replication process that could otherwise lead to harmful or fatal mutations in cells. Though ...

Recommended for you

Fighting bacteria—with viruses

4 hours ago

Research published today in PLOS Pathogens reveals how viruses called bacteriophages destroy the bacterium Clostridium difficile (C. diff), which is becoming a serious problem in hospitals and healthcare institutes, due to its re ...

Atomic structure of key muscle component revealed

5 hours ago

Actin is the most abundant protein in the body, and when you look more closely at its fundamental role in life, it's easy to see why. It is the basis of most movement in the body, and all cells and components ...

Brand new technology detects probiotic organisms in food

Jul 23, 2014

In the food industr, ity is very important to ensure the quality and safety of products consumed by the population to improve their properties and reduce foodborne illness. Therefore, a team of Mexican researchers ...

Protein evolution follows a modular principle

Jul 23, 2014

Proteins impart shape and stability to cells, drive metabolic processes and transmit signals. To perform these manifold tasks, they fold into complex three-dimensional shapes. Scientists at the Max Planck ...

Report on viruses looks beyond disease

Jul 22, 2014

In contrast to their negative reputation as disease causing agents, some viruses can perform crucial biological and evolutionary functions that help to shape the world we live in today, according to a new report by the American ...

User comments : 0