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.

The DNA encodes the entire genetic information required for building the proteins of the cell. Hence, DNA breaks disrupt the proteins and lead to changes in the cell function. These changes can lead to defects in the control of resulting in .

Using , researchers Prof. Batsheva Kerem and doctoral student Efrat Ozeri-Galai, of the Alexander Silverman Institute of Life Sciences in the Faculty of Science were able to characterize for the first time the DNA regions which are the most sensitive regions to breakage in early stages of cancer development. This is a breakthrough in our understanding of the effect of the DNA sequence and structure on its replication and stability.

"A hallmark of most human cancers is accumulation of damage in the DNA, which drives cancer development," says Prof. Kerem. "In the early stages of cancer development, the cells are forced to proliferate. In each cycle of proliferation the DNA is replicated to ensure that the have a full DNA. However, in these early stages the conditions for are perturbed, leading to DNA breaks, which occur specifically in regions defined as 'fragile sites'."

In this research Prof. Kerem and Ozeri-Galai used a sophisticated new methodology which enables the study of single , in order to study the basis for the specific sensitivity of the fragile sites. The findings are highly important since they shed new light on the DNA features and on the regulation of DNA replication along the first regions that break in cancer development.

The results show that along the fragile region there are sites that slow the DNA replication and even stop it. In order to allow completion of the DNA replication the cells activate already under normal conditions mechanisms that are usually used under stress. As a result, under conditions of replication stress, such as in early cancer development stages, the cell has no more tools to overcome the stress, and the DNA breaks.

The results of this study reveal the molecular mechanism that promotes cancer development. Currently, different studies focus on the very early stages of cancer development aiming to identify the events leading to cancer on the one hand and on their inhibition, on the other. The result of the current research identified for the first time DNA features that regulate DNA replication along the fragile sites, in early stages of cancer development. In the future, these findings could lead to the development of new therapeutic approaches to restrain and/or treat cancer.

Explore further: Two-armed control of ATR, a master regulator of the DNA damage checkpoint

Related Stories

Researchers demonstrate why DNA breaks down in cancer cells

May 03, 2011

Damage to normal DNA is a hallmark of cancer cells. Although it had previously been known that damage to normal cells is caused by stress to their DNA replication when cancerous cells invade, the molecular basis for this ...

Recommended for you

Japanese scientist resigns over stem cell scandal

5 hours ago

A researcher embroiled in a fabrication scandal that has rocked Japan's scientific establishment said Friday she would resign after failing to reproduce results of what was once billed as a ground-breaking study on ...

'Hairclip' protein mechanism explained

19 hours ago

Research led by the Teichmann group on the Wellcome Genome Campus has identified a fundamental mechanism for controlling protein function. Published in the journal Science, the discovery has wide-ranging implications for bi ...

User comments : 0

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.