Dynamic SUMO modification regulates mitotic chromosome assembly and cell cycle progression in Caenorhabditis elegans

Abstract

The small ubiquitin-like modifier (SUMO), initially characterized as a suppressor of a mutation in the gene encoding the centromeric protein MIF2, is involved in many aspects of cell cycle regulation. The dynamics of conjugation and deconjugation and the role of SUMO during the cell cycle remain unexplored. Here we used Caenorhabditis elegans to establish the contribution of SUMO to a timely and accurate cell division. Chromatin-associated SUMO conjugates increase during metaphase but decrease rapidly during anaphase. Accumulation of SUMO conjugates on the metaphase plate and proper chromosome alignment depend on the SUMO E2 conjugating enzyme UBC-9 and SUMO E3 ligase PIASGEI-17. Deconjugation is achieved by the SUMO protease ULP-4 and is crucial for correct progression through the cell cycle. Moreover, ULP-4 is necessary for Aurora BAIR-2 extraction from chromatin and relocation to the spindle mid-zone. Our results show that dynamic SUMO conjugation plays a role in cell cycle progression.

SUMOylation controls stem cell proliferation and regional cell death through Hedgehog signaling in planarians

“…Downregulation of Ubc9 leads to an increase in DSBs that are similarly distributed along the AP axis. Chromosomal abnormalities were also evident after Ubc9(RNAi), which is consistent with both defective DNA repair response and chromosomal segregation [21,[47][48][49]. We also noted that Ubc9 downregulation leads to DNA damage response that occurs in clusters in both anterior and posterior regions, suggesting there may be focus of cells that are more susceptible to accumulate DSB.…”

“…Previous studies have suggested knockdown of Ubc9 is a key regulator of G1/S phase transition through various mechanisms of action [25,28,42,44]. Additional findings suggest Ubc9 knockdown induces DNA damage and chromosomal abnormalities, which would block cells from passing the critical cell cycle checkpoints [21,[47][48][49]. Therefore, this blockage in G1 phase could also impair the progression of post-mitotic progeny that will negatively impact the maintenance of differentiated tissues.…”

Molecular Circuitry of the SUMO (Small Ubiquitin-like Modifier) Pathway in Controlling Sumoylation Homeostasis and Suppressing Genome Rearrangements

“…Moreover, overexpression of ULP2 (also known as SMT4) suppresses defects in chromosome condensation and segregation, suggesting its role in regulating chromosome segregation (10,12). This role of Ulp2 in chromosome segregation appears to be conserved in higher eukaryotes including Caenorhabditis elegans and human cells, although its targets are poorly known (13,14). Consistent with its nuclear function, Ulp2 has been shown to localize throughout the nucleus and occasionally the nucleolus (15,16).…”

Analysis of Small Ubiquitin-Like Modifier (SUMO) Targets Reflects the Essential Nature of Protein SUMOylation and Provides Insight to Elucidate the Role of SUMO in Plant Development

“…Another scenario, which is not necessarily mutually exclusive with that discussed above, is that the need for the SUMOylated form of a protein may be restricted to a very specific time window, in only specific cell types, and/or a specific state of the protein, and hence the level of the SUMOylated protein relative to that of the whole protein pool is often low. Mitotic and repair proteins are good examples where targets are modified only during the mitotic phase of dividing cells or only during DNA repair (Jackson and Durocher, 2013;Pelisch et al, 2014). The reversible nature of protein SUMOylation may contribute to this process.…”