J 2022

Role of Nse1 Subunit of SMC5/6 Complex as a Ubiquitin Ligase

KOLESÁR, Peter, Karel STEJSKAL, David POTĚŠIL, Johanne M MURRAY, Jan PALEČEK et. al.

Basic information

Original name

Role of Nse1 Subunit of SMC5/6 Complex as a Ubiquitin Ligase

Name in Czech

Úloha Nse1 podjednotky komplexu SMC5/6 v ubikvitinaci

Authors

KOLESÁR, Peter (703 Slovakia, belonging to the institution), Karel STEJSKAL (203 Czech Republic, belonging to the institution), David POTĚŠIL (203 Czech Republic, belonging to the institution), Johanne M MURRAY and Jan PALEČEK (203 Czech Republic, guarantor, belonging to the institution)

Edition

Cells, BASEL, MDPI, 2022, 2073-4409

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 6.000

RIV identification code

RIV/00216224:14310/22:00126432

Organization unit

Faculty of Science

DOI

UT WoS

000758383300001

Keywords in English

SMC5; 6; Nse1; ubiquitin ligase; ubiquitination; Ubc13; Mms2; Nse4 kleisin

Tags

Tags

International impact, Reviewed
Změněno: 10/10/2024 15:10, Ing. Martina Blahová

Abstract

V originále

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.

Links

GA18-02067S, research and development project
Name: Úloha Nse1/Nse3/Nse4, E3-ubikvitin ligásy, ve stabilitě genomu
Investor: Czech Science Foundation
LM2018127, research and development project
Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)
Investor: Ministry of Education, Youth and Sports of the CR
LQ1601, research and development project
Name: CEITEC 2020 (Acronym: CEITEC2020)
Investor: Ministry of Education, Youth and Sports of the CR
LTC20033, research and development project
Name: The SMC5/6 complex in nucleome organization (Acronym: Nukleom)
Investor: Ministry of Education, Youth and Sports of the CR, INTER-COST
90127, large research infrastructures
Name: CIISB II