A protein found in DNA replication complexes is also essential for ribosome biosynthesis, according to new results from Yi-Chieh Du and Bruce Stillman (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY). The findings imply that the biosynthesis of ribosomes is associated with the decision to enter the cell division cycle.
The authors identified proteins associated with the yeast origin recognition complex (ORC), a set of proteins that binds chromosomal origins of DNA replication. Among the proteins identified was Yph1p, a homologue of zebrafish pescadillo, mutations in which lead to cell proliferation defects. Yph1p was also found in complex with a variety of other proteins, including those involved in ribosome biogenesis, cell cycle regulation, and checkpoint control. “The first link to ribosome biosynthesis came from the finding of Erb1p in the Yph1p complex,” says Stillman. “Mutation of the mouse ERB1 orthologue leads to G1 arrest and alters ribosome biosynthesis.”
In vivo, Yph1p activity was required for proper 60S ribosome biogenesis and for normal progression during S-phase. Yph1p levels were high in proliferating cells, but declined as cells entered the quiescent phase. Newly synthesized Yph1p was required for cells to exit G0 and initiate cell division. Though Stillman admits the link between DNA replication and ribosome biosynthesis is speculative, he adds that it makes sense, as proliferation requires the replication of both the genome and the cellular machineries. ▪