Cohesin organizes chromatin loops at DNA replication factories (original) (raw)

  1. Arkaitz Ibarra1,6,
  2. Vincent Coulon2,
  3. Juan Casado-Vela3,8,
  4. Daniel Rico4,
  5. Ignacio Casal3,9,
  6. Etienne Schwob2,
  7. Ana Losada5,11 and
  8. Juan Méndez1,10
  9. 1DNA Replication Group, Spanish National Cancer Research Centre (CNIO), E-28029 Madrid, Spain;
  10. 2Institut de Génétique Moléculaire de Montpellier, CNRS-Université Montpellier 1 et 2, 34293 Montpellier, Cedex 5, France;
  11. 3Protein Technology Unit, Biotechnology Programme, Spanish National Cancer Research Centre (CNIO), E-28029 Madrid, Spain;
  12. 4Structural Computational Biology Group, Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), E-28029 Madrid, Spain;
  13. 5Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), E-28029 Madrid, Spain
  1. ↵6 These authors contributed equally to this work.

Abstract

Genomic DNA is packed in chromatin fibers organized in higher-order structures within the interphase nucleus. One level of organization involves the formation of chromatin loops that may provide a favorable environment to processes such as DNA replication, transcription, and repair. However, little is known about the mechanistic basis of this structuration. Here we demonstrate that cohesin participates in the spatial organization of DNA replication factories in human cells. Cohesin is enriched at replication origins and interacts with prereplication complex proteins. Down-regulation of cohesin slows down S-phase progression by limiting the number of active origins and increasing the length of chromatin loops that correspond with replicon units. These results give a new dimension to the role of cohesin in the architectural organization of interphase chromatin, by showing its participation in DNA replication.

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