In an article published in Genome Biology , scientists show that DNA replication not only ensures faithful duplication of the genome, but also helps reshape the three-dimensional organization of chromosomes in the nucleus. Using an approach combining biophysical modeling and molecular biology experiments in baker’s yeast, they reveal how replication forks influence genome structure at multiple scales.
A 3D model of the genome to test the role of replication forks
Before each cell division, the DNA must be completely duplicated so that each daughter cell receives an accurate copy of the genome. In eukaryotes, this duplication occurs during the S phase of the cell cycle and starts from several "origins" distributed along the genome. At each origin, two replication forks, known as "sister" forks, move in opposite directions and gradually duplicate the DNA while changing the way the chromosomes fold and organize themselves within the cell nucleus.
In this study published in the journal Genome Biology, scientists focused on these structural effects of replication.
They developed an interdisciplinary strategy combining biophysical modeling and molecular biology experiments to explore the influence of replication on chromosome folding in baker’s yeast, a model organism often used for this type of study.
By integrating a realistic description of the 3D architecture of the yeast genome and the chronology of its replication into a numerical model, they were able to test different hypotheses about the behavior of replication forks and predict their impacts on chromosome organization at several scales.
From local fountain to global wave: spatial organization orchestrated by replication
Their model indicates that, at the local level, interactions between the two forks originating from the same source should leave a clearly identifiable signature in the data: "fountains" of contacts, which spread out from the origins and correspond to the dynamic formation of DNA loops guided by sister forks. Through new experiments conducted under different conditions, they have confirmed the existence of these fountains in vivo.
According to a CNRS communication dated December 23, 2025. Based on a scientific publication in Genome Biology to which Dario D’Asaro, Jean-Michel Arbona, Vinciane Piveteau, Aurèle Piazza, Cédric Vaillant, and Daniel Jost, members of the Laboratory of Biology and Modeling of the Cell (CNRS/ENS Lyon/INSERM/Univ Lyon 1), contributed: "Genome-wide modeling of DNA replication in space and time confirms the emergence of replication-specific patterns in vivo in eukaryotes." Thumbnail credit © Dario D’Asaro
Reference
D’Asaro D, Arbona JM, Piveteau V, Piazza A, Vaillant C, Jost D. Genome-wide modeling of DNA replication in space and time confirms the emergence of replication specific patterns in vivo in eukaryotes. Genome Biol. 2025 Dec 22;26(1):431. DOI: 10.1186/s13059-025-03872-4