A minimal rDNA array replicates early, delays genome replication, and uncouples anaphase entry from S phase completion

Kwan, E. X.; Alvino, G. M.; Lynch, K. L.; Levan, P. F.; Amemiya, H. M.; Wang, X. S.; Johnson, S. A.; Sanchez, J. C.; Miller, M. A.; Croy, M.; Lee, S.-b. B.; Naushab, M.; Cuperus, J.; Brewer, B. J.; Queitsch, C.; Raghuraman, M. K.

doi:10.1101/2021.02.25.432950

bioRxiv · 10.1101/2021.02.25.432950

A minimal rDNA array replicates early, delays genome replication, and uncouples anaphase entry from S phase completion

Kwan, E. X.·Alvino, G. M.·Lynch, K. L.·Levan, P. F.·Amemiya, H. M.·Wang, X. S.·Johnson, S. A.·Sanchez, J. C.·Miller, M. A.·Croy, M.·Lee, S.-b. B.·Naushab, M.·Cuperus, J.·Brewer, B. J.·Queitsch, C.·Raghuraman, M. K.

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Abstract

Eukaryotes maintain hundreds of copies of ribosomal DNA (rDNA), many more than required for ribosome biogenesis, suggesting a yet undefined role for large rDNA arrays outside of ribosomal RNA synthesis. We demonstrate that reducing the Saccharomyces cerevisiae rDNA array to 35 copies, which is sufficient for ribosome function, shifts rDNA from being the latest replicating region in the genome to one of the earliest. This change in replication timing results in delayed genome-wide replication and classic replication defects. We present evidence that the requirement for rDNA to replicate late, which is conserved among eukaryotes, also coordinates the completion of genome replication with anaphase entry through the proper sequestration of the mitotic exit regulator Cdc14p in the rDNA-containing nucleolus. Our findings suggest that, instead of being a passive repetitive element, the large late-replicating rDNA array plays an active role in genome replication and cell cycle control.

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Kwan, E. X., Alvino, G. M., Lynch, K. L., Levan, P. F., Amemiya, H. M., Wang, X. S., Johnson, S. A., Sanchez, J. C., Miller, M. A., Croy, M., Lee, S.-b. B., Naushab, M., Cuperus, J., Brewer, B. J., Queitsch, C., Raghuraman, M. K.. 2021-02-25. A minimal rDNA array replicates early, delays genome replication, and uncouples anaphase entry from S phase completion. https://doi.org/10.1101/2021.02.25.432950

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