A tetrapyrrole-regulated ubiquitin ligase controls algal nuclear DNA replication

In plant cells, organelle DNA replication (ODR) is coordinated with nuclear DNA replication (NDR), with ODR preceding NDR during cell cycle progression. We previously showed that the occurrence of ODR is signalled by a tetrapyrrole compound, most likely Mg-protoporphyrin IX (Mg-ProtoIX), resulting in the activation of cyclin-dependent kinase A (CDKA) and consequent initiation of NDR (refs 1, 2, 3). Here we identify an F-box protein of SCF-type E3 ubiquitin ligase (Fbx3) in the red alga Cyanidioschyzon merolae, which inhibits CDKA by ubiquitylating the relevant cyclin and inducing its degradation. Mg-ProtoIX binds to Fbx3 and inhibits cyclin ubiquitylation. Thus, these observations indicate that Fbx3 serves as the receptor for the plastid-to-nucleus retrograde signal Mg-ProtoIX and thereby contributes to a checkpoint mechanism ensuring coordination of ODR and NDR.