| Autor: |
Courtot L; Centre de Recherches en Cancérologie de Toulouse (CRCT), UMR1037 Inserm, University Paul Sabatier III, ERL5294 CNRS, 2 Avenue Hubert Curien, 31037 Toulouse, France., Bournique E; Centre de Recherches en Cancérologie de Toulouse (CRCT), UMR1037 Inserm, University Paul Sabatier III, ERL5294 CNRS, 2 Avenue Hubert Curien, 31037 Toulouse, France., Maric C; Université de Paris, CNRS, Institut Jacques Monod, DNA Replication Pathologies Team, F-75006 Paris, France., Guitton-Sert L; Centre de Recherches en Cancérologie de Toulouse (CRCT), UMR1037 Inserm, University Paul Sabatier III, ERL5294 CNRS, 2 Avenue Hubert Curien, 31037 Toulouse, France., Madrid-Mencía M; Centre de Recherches en Cancérologie de Toulouse (CRCT), UMR1037 Inserm, University Paul Sabatier III, ERL5294 CNRS, 2 Avenue Hubert Curien, 31037 Toulouse, France., Pancaldi V; Centre de Recherches en Cancérologie de Toulouse (CRCT), UMR1037 Inserm, University Paul Sabatier III, ERL5294 CNRS, 2 Avenue Hubert Curien, 31037 Toulouse, France.; Barcelona Supercomputing Center, 08034 Barcelona, Spain., Cadoret JC; Université de Paris, CNRS, Institut Jacques Monod, DNA Replication Pathologies Team, F-75006 Paris, France., Hoffmann JS; Laboratoire de pathologie, Laboratoire d'excellence Toulouse Cancer, Institut Universitaire du Cancer-Toulouse, Oncopole, 1 Avenue Irène-Joliot-Curie, CEDEX, 31059 Toulouse, France., Bergoglio V; Centre de Recherches en Cancérologie de Toulouse (CRCT), UMR1037 Inserm, University Paul Sabatier III, ERL5294 CNRS, 2 Avenue Hubert Curien, 31037 Toulouse, France. |
| Abstrakt: |
DNA replication timing (RT), reflecting the temporal order of origin activation, is known as a robust and conserved cell-type specific process. Upon low replication stress, the slowing of replication forks induces well-documented RT delays associated to genetic instability, but it can also generate RT advances that are still uncharacterized. In order to characterize these advanced initiation events, we monitored the whole genome RT from six independent human cell lines treated with low doses of aphidicolin. We report that RT advances are cell-type-specific and involve large heterochromatin domains. Importantly, we found that some major late to early RT advances can be inherited by the unstressed next-cellular generation, which is a unique process that correlates with enhanced chromatin accessibility, as well as modified replication origin landscape and gene expression in daughter cells. Collectively, this work highlights how low replication stress may impact cellular identity by RT advances events at a subset of chromosomal domains. |
