The origin-recognition complex (ORC) is a molecular landing pad. At various times during the cell division cycle, ORC nucleates the assembly of appropriate protein complexes at replication origins. For this reason, a search for proteins that interact with ORC is often used to uncover new components of the DNA-replication machinery. But, as they report in Cell, when Yi-Chieh Du and Bruce Stillman carried out such a search, they identified a protein that seems to be involved in more than just DNA replication.

Du and Stillman started with immunoprecipitation experiments to identify proteins that interact with ORC. Seven proteins were specifically precipitated from wild-type yeast whole-cell extracts, but not from orc2-1 mutant extracts, one of which was identical to yeast Yph1. Yph1 contains a BRCT domain, as well as a putative nuclear-localization signal, and is localized mainly in — or near to — the nucleolus.

Reciprocal immunoprecipitation experiments confirmed that Yph1 and ORC interact both in vitro and in vivo, but also showed that several other proteins interact with Yph1. To analyse these complexes, the authors separated them by glycerol-gradient sedimentation, followed by western blotting. Two main complexes were detected, and mass-spectrometry analysis showed that the smaller one contained Yph1, Erb1 and Ytm1. The larger complex contained these proteins, but also trapped factors that are involved in cell-cycle regulation, checkpoint control, ribosome biosynthesis and chromatin remodelling.

Both Erb1 and Ytm1 are involved in biosynthesis of the 60S ribosomal subunit, and Ytm1 is also essential for the G1–S transition. So, Du and Stillman next investigated the ribosome profile of a temperature-sensitive Yph1 mutant strain (yph1-td). They could not detect free 60S ribosomal subunits in the yph1-td cells, which indicates that Yph1 is needed for the synthesis or stability of this subunit.

How might this role for Yph1 in ribosome biogenesis link to its possible function in DNA replication? The authors noticed that the levels of Yph1 varied in cells that were grown under different conditions, and showed that there is a correlation between the levels of Yph1 and the rate of proliferation that occurs in response to the energy source that is used. So, levels of Yph1 are high when glucose is plentiful and proliferation is high, but low (or absent) when slow proliferation occurs due to poor energy sources.

When these findings are combined, a picture emerges in which Yph1 might help to link processes that require high levels of energy — for example, DNA replication and ribosome biogenesis — to a regulatory mechanism that senses the amount of an available energy source. Elegant though this explanation is, however, the authors point out that Yph1 could turn out to be involved in these processes independently.