The mystery of how cells package their DNA and how it relates to cancer, the topic of CNIO’s next international congress

Our cells know how to solve the problem that tortures us when we pack a suitcase: how to put in what obviously does not fit, or will only fit if folded and organized to perfection. Cells fold and organize to perfection their DNA, which in our species, when stretched, extends to two meters.

Investigating this meticulous folding is of interest because, as has been discovered in recent years, errors in the three-dimensional structure of the genome are directly related to cancer.

The latest results on the study of the genome’s 3D structure, and how it relates to genome stability, will be discussed by twenty international leaders in this area at the CNIO-CaixaResearch Frontiers Meeting ‘Genome Organisation and Stability’, to be held in collaboration with La Caixa on May 22 and 23.

Two meters of DNA packaged in each cell

All cells have in their nucleus several DNA molecules, the chromosomes, which contain the genes – the instructions for building and running an organism. If these molecules were simply compressed into a ball, the resulting tangle would be larger than the cell. So how exactly does DNA fold up to fit? How exactly does DNA fit into the nucleus of cells?

This is a booming area of research. It is now known that the 3D shape DNA takes on determines how genes are expressed -because distant areas of the molecule come into contact.

Also, understanding DNA folding will help identify the most fragile and unstable areas of the genome, those most susceptible to rearrangements of the genetic material. Genome instability leads to failures in the cell –such as an abnormal number of chromosomes– directly linked to cancer.

Simulation of the structure of chromosomes in 3-D. / Credit: M. Di Stefano and C. Micheletti, SISSA.

“Extraordinary attention in recent years”

“The three-dimensional folding [of DNA] in the cell nucleus determines how cells read, interpret and maintain the information in the genome. Its study has attracted extraordinary attention in the last few years,” say the conference organizers, CNIO researchers Felipe Cortés, Ana Losada and Óscar Fernández-Capetillo,as well as Andre Nussenzweig, from the U.S. National Cancer Institute.

“The most illustrative example for this is perhaps the regulation of gene expression, which is now unconceivable to understand without taking into account how the genome is structurally organised”, they say. “The connections between 3D genome organisation and the processes that signal and repair DNA damage are, however, only now starting to emerge, and proving fundamental to understand the endogenous sources of DNA breaks and chromosomal rearrangement events that drive cancer onset and progression. In this meeting we aim at bringing together world-leading researchers in both fields, 3D genome organisation and the DNA-damage response, in order to provide an ideal setting to bridge the gap between these two fundamental aspects of genome dynamics”.

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Program: CNIO-CaixaResearch Frontiers Meeting: Genome Organization and Stability #CFM_Genome – CNIO