Temporal regulation of DNA replication in mammalian cells

Abstract

Eukaryotic cells follow a temporal program to duplicate their genomes. Chromosomes are divided into domains with a specific DNA replication timing (RT), not dictated by DNA sequence alone, which is conserved from one cell cycle to the next. Timing of replication correlates with gene density, transcriptional activity, chromatin structure and nuclear position, making it an intriguing epigenetic mark. The differentiation from embryonic stem cells to specialized cell types is accompanied by global changes in the RT program. This review covers our current understanding of the mechanisms that determine RT in mammalian cells, its possible biological significance and how unscheduled alterations of the RT program may predispose to human disease.

Keywords::

• Chromosome domain
• epigenetics
• histone acetylation
• nuclear position
• replication timing

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Erratum

Acknowledgement

I apologize to authors whose work is not cited directly, particularly those who study replication timing in non-mammalian organisms. I am grateful to Tomás Aparicio for the immunofluorescence images used in Figure 1; Arkaitz Ibarra and Almudena R. Ramiro for useful comments on the manuscript, and all members of my laboratory for many discussions. Our research is funded by the Spanish Ministry of Science and Innovation (BFU2007-65326 and CSD2007-0015), the European Union (Marie Curie IRG FP6-031129) and Fundación Caja Madrid.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Editor: Michael M. Cox