Role of Nse1 Subunit of SMC5/6 Complex as a Ubiquitin Ligase
| Authors | |
|---|---|
| Year of publication | 2022 |
| Type | Article in Periodical |
| Magazine / Source | Cells |
| MU Faculty or unit | |
| Citation | |
| Web | https://www.mdpi.com/2073-4409/11/1/165 |
| Doi | http://dx.doi.org/10.3390/cells11010165 |
| Keywords | SMC5; 6; Nse1; ubiquitin ligase; ubiquitination; Ubc13; Mms2; Nse4 kleisin |
| Description | Structural Maintenance of Chromosomes (SMC) complexes are important for many aspects of the chromosomal organization. Unlike cohesin and condensin, the SMC5/6 complex contains a variant RING domain carried by its Nse1 subunit. RING domains are characteristic for ubiquitin ligases, and human NSE1 has been shown to possess ubiquitin-ligase activity in vitro. However, other studies were unable to show such activity. Here, we confirm Nse1 ubiquitin-ligase activity using purified Schizosaccharomyces pombe proteins. We demonstrate that the Nse1 ligase activity is stimulated by Nse3 and Nse4. We show that Nse1 specifically utilizes Ubc13/Mms2 E2 enzyme and interacts directly with ubiquitin. We identify the Nse1 mutation (R188E) that specifically disrupts its E3 activity and demonstrate that the Nse1-dependent ubiquitination is particularly important under replication stress. Moreover, we determine Nse4 (lysine K181) as the first known SMC5/6-associated Nse1 substrate. Interestingly, abolition of Nse4 modification at K181 leads to suppression of DNA-damage sensitivity of other SMC5/6 mutants. Altogether, this study brings new evidence for Nse1 ubiquitin ligase activity, significantly advancing our understanding of this enigmatic SMC5/6 function. |
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