Molecular Cell.

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The molecular basis for the breakage of DNA – the hallmark of cancer cells – has been identified by Hebrew University of Jerusalem scientists. The important discovery will be published on Friday in the prestigious journalThe DNA encodes all the genetic information needed to build the cell’s proteins. Thus, breaks in the DNA disrupt the proteins and lead to changes in cell function. These changes can lead to defects in the control of cellular proliferation, which results in the development of cancer.Using cutting-edge technologies, researchers Prof. Batsheva Kerem and doctoral student Efrat Ozeri-Galai, of the Alexander Silverman Institute of Life Sciences in the HU’s Faculty of Science, were able to characterize for the first time the DNA regions that are the most sensitive 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, they said on Thursday.“A hallmark of most human cancers is accumulation of damage in the DNA, which drives cancer development,” Kerem said. “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 daughter cells have a full DNA. However, in these early stages the conditions for DNA replication are perturbed, leading to DNA breaks, which occur specifically in regions defined as ‘fragile sites.’”In their research, the team used a sophisticated new methodology that enables the study of single DNA molecules to study the basis for the specific sensitivity of the fragile sites. The findings are very important, as they shed new light on the DNA features and the regulation of DNA replication along the first regions that break in the development of cancer.The results show that along the fragile region, there are sites that slow the DNA replication and even stop it. To allow completion of the DNA replication, already under normal conditions the cells activate 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.This study revealed the molecular mechanism that promotes cancer development, they said.Currently, other studies focus on the very early stages of cancer development, aiming to identify the events leading to cancer on the one hand and to its inhibition, on the other. 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, they hope, these findings could lead to the development of new therapeutic approaches to restrain and/or treat cancer.