The Role of Cid13 in the G1/S Checkpoint in Fission Yeast

Abstract

This study was carried out at the Department of Cell Biology at the Institute of Cancer Research at the Oslo University Hospital as a part of my Master’s degree in molecular biosciences at the University of Oslo. Our group is working with cell cycle studies in fission yeast Schizosaccaromyces pombe and the main focus is on the G1/S checkpoint which was recently characterized. This checkpoint is activated in G1 phase in response to ultraviolet C (UVC) irradiation which delays the cell-cycle progression in late G1.

The G1/S checkpoint is dependent on the Gcn2 kinase which phosphorylates eukaryotic translation initiation factor eIF2α and this phosphorylation leads to downregulation of general translation. Despite the general downregulation of translation some mRNAs are still translated normally or even at an increased rate after UVC irradiation.

One of these mRNAs is cid13 and here we explore the importance of Cid13 in response to UVC irradiation in G1. Cid13 belongs to a family of poly(A) polymerases and its only known target is the mRNA of suc22, the small subunit of ribonucleotide reductase (RNR). Cytoplasmic polyadenylation is known to increase mRNA half-life leading to increased translation. Cid13 has been suggested to regulate dNTP production by increasing the amount of Suc22 and therefore the total amount of RNR in the cells. RNR is regulated on several levels but no translational regulation has been identified so far.

Here we show that deletion of cid13 leads to loss of G1/s checkpoint and increased UVC sensitivity. We also show that Suc22 levels are increased in a Cid13 dependent manner after UVC irradiation. However, the levels of dNTPs do not show a corresponding increase. These observations led us to conclude that Cid13 must have other targets important for an appropriate response to UVC irradiation in G1.