Ulp2 and the DNA damage response - Desumoylation enables safe passage through mitosis

The DNA damage checkpoint is a crucial defense mechanism used by cells to withstand DNA damage. Activation of the checkpoint halts the cell cycle at metaphase and allows time for DNA repair prior to cell division. Much effort has been placed on identifying the proteins involved in checkpoint activation and how they elicit the damage response, whereas much less is known about how the checkpoint is silenced and cell division resumes. We recently reported that Ulp2, a SUMO protease, is required for cell division following termination of the DNA damage checkpoint in budding yeast. Here we discuss potential mechanisms by which Ulp2 enables the successful completion of mitosis following DNA damage. We also suggest candidate Ulp2 substrates whose desumoylation may be necessary for cell cycle restart. Finally, given the requirement of Ulp2 for survival in the presence of various metaphase-arresting agents, we suggest that the necessity for Ulp2 following checkpoint termination may not be specific to the DNA-damage response, but rather may indicate a broader role for desumoylation following prolonged metaphase arrest.