Ribosomal DNA replication time coordinates completion of genome replication and anaphase in yeast

Timely completion of genome replication is a prerequisite for mitosis, genome integrity, and cell survival. A challenge to this timely completion comes from the need to replicate the hundreds of untranscribed copies of rDNA that organisms maintain in addition to the copies required for ribosome biogenesis. Replication of these rDNA arrays is relegated to late S phase despite their large size, repetitive nature, and essentiality. Here, we show that, in Saccharomyces cerevisiae, reducing the number of rDNA repeats leads to early rDNA replication, which results in delaying replication elsewhere in the genome. Moreover, cells with early-replicating rDNA arrays and delayed genome-wide replication aberrantly release the mitotic phospha-tase Cdc14 from the nucleolus and enter anaphase prematurely. We propose that rDNA copy number determines the replication time of the rDNA locus and that the release of Cdc14 upon completion of rDNA replication is a signal for cell cycle progression.

Automated summary

Timely completion of genome replication is crucial for mitosis, genome integrity, and cell survival. However, the replication of untranscribed rDNA poses a challenge to this process. By reducing the number of rDNA repeats in Saccharomyces cerevisiae, we observed early replication of rDNA, which subsequently delayed replication of other regions in the genome. Furthermore, cells with early-replicating rDNA and delayed genome-wide replication prematurely released the mitotic phosphatase Cdc14, leading to premature entry into anaphase. We propose that rDNA copy number determines the replication time of rDNA and the release of Cdc14 signals cell cycle progression.