Heterochromatin DNA replication and Rif1

Constitutive heterochromatin is essential for chromosome maintenance in all eukaryotes. However, the repetitive nature of the underlying DNA, the presence of very stable protein–DNA complexes and the highly compacted nature of this type of chromatin represent a challenge for the DNA replication machinery. Data collected from different model organisms suggest that at least some of the components of the DNA replication checkpoint could be essential for ensuring the completion of DNA replication in the context of heterochromatin. I review and discuss the literature that directly or indirectly contributes to the formulation of this hypothesis. In particular, I focus my attention on Rif1, a newly discovered member of the DNA replication checkpoint. Recent data generated in mammalian cells highlight the spatial and temporal relation between Rif1, pericentromeric heterochromatin and S-phase. I review these recent and the previous data coming from studies performed in yeast in order to highlight the possible evolutionary conserved links and propose a molecular model for Rif1 role in heterochromatin replication.