The cell cycle and protein synthesis: Serendipity, stupidity and surprises

Speaker: Professor Erik Boye, Institute for Cancer Research, Montebello, Oslo, Norway

Host: Professor Olaf Nielsen, Functional Genomics, BIO-UCPH

Erik Boye is a visiting professor at the Department of Biology from September 1st to December 31st 2017 (fundet by the Lundbeck Foundation).

Abstract
Progression of the cell cycle is regulated by a number of complex pathways and protein modifications. We started out to study what happens to cell-cycle progression when fission yeast cells are stressed in G1 phase. In this presentation I shall emphasize how such a simple starting point can lead to important discoveries and a multitude of new projects, since every journey into unknown terrain will inevitably pass by important clues and novel information.  We discovered a novel G1-S checkpoint that stopped the cell cycle after exposure to ultraviolet light, UV1. This checkpoint is distinct from any classic checkpoint and depends upon the stress kinase Gcn2 and on Gcn2 phosphorylating the translation initiation factor eIF2α2. Consistent with the accepted role of eIF2α phosphorylation, we found that the dose of UV that we employed shut down translation. However, in disagreement with textbooks and general consensus in the field, the inhibition of translation was found to be independent of Gcn2 and of eIF2α phosphorylation3. This was found to be true for fission yeast, budding yeast and for mammalian cells, which makes it likely that there is a hitherto undescribed mechanism of translational regulation and that this mechanism is conserved through evolution. Furthermore, the data questions the dogma that phosphorylation of eIF2α is the main regulator of translation. Our recent data suggest that a high level of eIF2α is neither sufficient nor required to downregulate translation.