Fission yeast neddylation ligase Dcn1 facilitates cohesin cleavage and chromosome segregation at anaphase

Abstract

Post-translational protein modification such as phosphorylation and ubiquitination are critical during mitosis to ensure proper timing and progression of chromosome segregation. It has been recently recognized that another type of protein modification – neddylation – may also regulate mitosis and chromosome segregation. The conserved protein DCN1 (defective cullin neddylation 1) has been shown, when knocked-down by RNAi, to result in multinucleated cells and/or blockage of cell proliferation. However, how DCN1 functions in mitosis and chromosome segregation is not known. We report here the fission yeast dcn1+ and its role in mitosis and chromosome segregation. Dcn1-GFP localizes to the nucleus throughout the cell cycle. dcn1-deletion (dcn1Δ) leads to chromosome and kinetochore lagging at anaphase, resulting from delayed and attenuated cohesin cleavage and sister chromatids separation. These results put Dcn1 upstream of the anaphase promoting complex/cyclosome (APC/C) pathway. We propose a mechanism for Dcn1 function at mitosis.

Keywords

• Chromosome segregation
• Mitosis
• Neddylation