Impact of Chromosomal Context on Origin Selection and the Replication Program

Autor: Lilian Lanteri, Anthony Perrot, Diane Schausi-Tiffoche, Pei-Yun Jenny Wu
Přispěvatelé: Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Marie Curie Career Integration Grant from the 7th Framework Programme of the European Commission [334200], Chair for Emergence, Science, and Society program of the Region Nouvelle Aquitaine, Ligue Contre le Cancer Grand-Ouest, Fondation ARC
Rok vydání: 2022
Předmět:
Zdroj: Genes
Genes, 2022, 13 (7), pp.1244. ⟨10.3390/genes13071244⟩
Genes; Volume 13; Issue 7; Pages: 1244
ISSN: 2073-4425
DOI: 10.3390/genes13071244⟩
Popis: International audience; Eukaryotic DNA replication is regulated by conserved mechanisms that bring about a spatial and temporal organization in which distinct genomic domains are copied at characteristic times during S phase. Although this replication program has been closely linked with genome architecture, we still do not understand key aspects of how chromosomal context modulates the activity of replication origins. To address this question, we have exploited models that combine engineered genomic rearrangements with the unique replication programs of post-quiescence and pre-meiotic S phases. Our results demonstrate that large-scale inversions surprisingly do not affect cell proliferation and meiotic progression, despite inducing a restructuring of replication domains on each rearranged chromosome. Remarkably, these alterations in the organization of DNA replication are entirely due to changes in the positions of existing origins along the chromosome, as their efficiencies remain virtually unaffected genome wide. However, we identified striking alterations in origin firing proximal to the fusion points of each inversion, suggesting that the immediate chromosomal neighborhood of an origin is a crucial determinant of its activity. Interestingly, the impact of genome reorganization on replication initiation is highly comparable in the post-quiescent and pre-meiotic S phases, despite the differences in DNA metabolism in these two physiological states. Our findings therefore shed new light on how origin selection and the replication program are governed by chromosomal architecture.
Databáze: OpenAIRE
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