Related Experiment Video
Updated: Jul 8, 2026
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
Ulp2 and the DNA damage response: desumoylation enables safe passage through mitosis
Rachael Felberbaum1, Mark Hochstrasser
1Department of Molecular, Cell, & Developmental Biology, Yale University, New Haven, Connecticut, USA.
Abstract:
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.
Insights
The SUMO protease Ulp2 is essential for cell division after DNA damage checkpoints are deactivated in budding yeast. This finding suggests desumoylation by Ulp2 plays a broader role in cell cycle restart after metaphase arrest.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The DNA damage checkpoint is a vital cellular mechanism that halts the cell cycle at metaphase to allow DNA repair.
- While checkpoint activation is well-studied, the mechanisms for checkpoint silencing and cell cycle resumption are less understood.
Purpose of the Study:
- To investigate the role of Ulp2, a SUMO protease, in enabling cell division after DNA damage checkpoint termination.
- To identify potential Ulp2 substrates involved in cell cycle restart following DNA damage.
Main Methods:
- The study focused on budding yeast (Saccharomyces cerevisiae).
- Investigated the function of Ulp2, a SUMO protease, in the context of DNA damage response and cell cycle progression.
Main Results:
- Ulp2 is required for cell division subsequent to the termination of the DNA damage checkpoint.
- Identified potential substrates of Ulp2 whose desumoylation is critical for cell cycle restart.
- Ulp2 is also necessary for survival when cells are exposed to various metaphase-arresting agents.
Conclusions:
- Ulp2 facilitates successful mitosis completion after DNA damage.
- Desumoylation by Ulp2 may be a general requirement for cell cycle restart after prolonged metaphase arrest, not limited to DNA damage response.
Related Concept Videos
02:36DNA Damage can Stall the Cell Cycle
02:36DNA Damage Can Stall the Cell Cycle
02:23Abnormal Proliferation
02:10Translesion DNA Polymerases
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
01:38Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
01:08Nucleotide Excision Repair