Choreography of DNA replication: Yap and Rif1 lead the dance!

In multicellular eukaryotic organisms, genomic DNA replicates in a temporally controlled manner with regions of early, intermediate, or late replication. This coordination is called the replication timing program, which is cell type specific and dynamically regulated during development. How it is orchestrated is poorly understood, but its deregulation causes genomic instability and is observed in many diseases. The identification of the factors controlling this program is therefore essential.

Two teams from I2BC and NeuroPSI have collaborated to address this topic using different facets of the Xenopus model: an in vitro system of replication in egg extracts, and in vivo approaches of loss of function during early embryonic divisions and in retinal neural stem cells. This study reveals a novel, non-transcriptional role for Yap, an effector of the Hippo signaling pathway, in the regulation of replication dynamics and shows that Yap interacts with Rif1, the primary regulator of the replication timing program. The teams propose a model in which Yap and Rif1 work in concert as brakes to control the execution of the DNA replication program, allowing finely regulated and accurate replication during embryonic development and in post-embryonic stem cells.

A non-transcriptional function of Yap regulates the DNA replication program in Xenopus laevis. Rodrigo Meléndez García, Olivier Haccard, Albert Chesneau, Hemalatha Narassimprakash, Jérôme Roger, Muriel Perron, Kathrin Marheineke, Odile Bronchain.

Article published in eLifeAccess to the manuscript