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Researchers from IBMB-CSIC decipher the first level of DNA folding

05.10.2018

DNA topology team from the Structural Biology Unit (SBU) of the Institute of Molecular Biology of Barcelona (IBMB-CSIC) at  the Barcelona Science Park has solved the so-called “paradox of the nucleosomal DNA linking number”. They have been able to show that the theory described about how DNA is packaged in our cells was true. The solution to this problem, which has been the subject of debate for more than 3 decades, has been published in the journal Nature Communications.

 

Prof. Joaquim Roca with the DNA topology Lab's team: Ofelia Díaz, Sílvia Dyson, Joana Segura, Antonio Valdes and Belén Martínez (Photo: IBMB-CSIC).

The nucleosome is a complex of DNA and histone proteins, which constitutes the first degree of DNA packaging within the cell. In each nucleosome, about 146 base pairs of DNA envelop an octamer of histones. The distribution of this structure over thousands or millions of DNA base pairs generates a fiber similar to a string of beads. The folding of DNA in nucleosomes allows to reduce more than four times the length of the DNA molecules and make them in turn much more flexible, which is fundamental so that they can be organized into chromosomes and distributed in an orderly manner within the cell nucleus.

The so-called “paradox of the nucleosomal DNA linking number” refers to an incongruity in the way in which DNA is folded to form nucleosomes, which are the structural and fundamental unit of chromosomes. “What had been described theoretically did not coincide with the results obtained so far. We have applied a new strategy to calculate with great precision the number of double helix crosslinks in the nucleosomes under physiological conditions “, explains Prof. Joaquim Roca, head of the DNA Topology Lab

“We have examined the topology of more than 1000 nucleosomes within the cell. The new methodology has allowed us to discover a different value for the number of cross-links from that which had been assumed as correct in previous studies”says Joana Segura, first author of the project.

The new value obtained in the DNA Topology laboratory solves the “linking number paradox” of the DNA packaging. At the same time, it deciphers the first level of DNA folding, which is the molecule that contains all our genetic information. This advance put new bases to the study on how DNA is packaged in order to store all the information necessary for life within a space as small as the cell nucleus.

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► Reference article
Joana Segura, Ricky S. Joshi, Ofelia Díaz-Ingelmo, Antonio Valdés, Silvia Dyson, Belén Martínez-García and Joaquim Roca "Intracellular nucleosomes constrain a DNA linking number difference of -1.26 that reconciles the Lk paradox". Nature Communications (2018) DOI: 10.1038/s41467-018-06547-w