Linking the organization of DNA replication with genome maintenance
The spatial and temporal organization of genome duplication, also referred to as the replication program, is defined by the distribution and the activities of the sites of replication initiation across the genome. Alterations to the replication profile are associated with cell fate changes during development and in pathologies, but the importance of undergoing S phase with distinct and specific programs remains largely unexplored. We have recently addressed this question, focusing on the interplay between the replication program and genome maintenance. In particular, we demonstrated that when cells encounter challenges to DNA synthesis, the organization of DNA replication drives the response to replication stress that is mediated by the ATR/Rad3 checkpoint pathway, thus shaping the pattern of genome instability along the chromosomes. In this review, we present the major findings of our study and discuss how they may bring new perspectives to our understanding of the biological importance of the replication program.
KeywordsDNA replication Replication program S phase checkpoint Genome instability Replication stress DNA damage Rad3/ATR (ataxia telangiectasia and Rad3-related) Fission yeast
We thank Damien Coudreuse for critical reading of the manuscript. This work was supported by funding from the Institut National du Cancer (INCA, PLBIO 15-043) and the Région Bretagne. We apologize to any authors whose work was not cited due to space restrictions.
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Conflict of interest
The authors declare that they have no conflict of interest.