The (elusive) role of the SMC5/6 complex

Fernández-Capetillo, Óscar

doi:10.1080/15384101.2015.1137713

Cited by 7 publications

(4 citation statements)

References 7 publications

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“…The catalytic activity of SMC5/6 is provided by the E3 SUMO-protein ligase NSE2 (Fernandez-Capetillo, 2016), and is essential to globally facilitate the resolution of intermediates during homologous sister chromatid recombination (Bermúdez-López et al, 2010; Chavez et al, 2010), which unresolved may also cause anaphase bridges (Chan et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Arabidopsis NSE4 Proteins Act in Somatic Nuclei and Meiosis to Ensure Plant Viability and Fertility

et al. 2019

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The SMC 5/6 complex together with cohesin and condensin is a member of the structural maintenance of chromosome (SMC) protein family. In non-plant organisms SMC5/6 is engaged in DNA repair, meiotic synapsis, genome organization and stability. In plants, the function of SMC5/6 is still enigmatic. Therefore, we analyzed the crucial δ-kleisin component NSE4 of the SMC5/6 complex in the model plant Arabidopsis thaliana . Two functional conserved Nse4 paralogs ( Nse4A and Nse4B ) are present in A. thaliana , which may have evolved via gene subfunctionalization. Due to its high expression level, Nse4A seems to be the more essential gene, whereas Nse4B appears to be involved mainly in seed development. The morphological characterization of A. thaliana T-DNA mutants suggests that the NSE4 proteins are essential for plant growth and fertility. Detailed investigations in wild-type and the mutants based on live cell imaging of transgenic GFP lines, fluorescence in situ hybridization (FISH), immunolabeling and super-resolution microscopy suggest that NSE4A acts in several processes during plant development, such as mitosis, meiosis and chromatin organization of differentiated nuclei, and that NSE4A operates in a cell cycle-dependent manner. Differential response of NSE4A and NSE4B mutants after induced DNA double strand breaks (DSBs) suggests their involvement in DNA repair processes.

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Section: Discussionmentioning

confidence: 99%

Arabidopsis NSE4 Proteins Act in Somatic Nuclei and Meiosis to Ensure Plant Viability and Fertility

et al. 2019

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“…It has been speculated that the SMC5/6 complex concentrates around different types of joint molecules, such as SCI, stalled forks and DNA repair intermediates, and recruits complexes involved in their resolution (43). Murine and human cells depleted of SMC5 or SMC6 accumulate chromatid-linking anaphase bridges (20,44).…”

Section: Discussionmentioning

confidence: 99%

A genome-wide RNAi screen identifies the SMC5/6 complex as a non-redundant regulator of a Topo2a-dependent G2 arrest

Deiss

Lockwood

Howell

et al. 2018

Nucleic Acids Research

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The Topo2a-dependent arrest is associated with faithful segregation of sister chromatids and has been identified as dysfunctional in numerous tumour cell lines. This genome-protecting pathway is poorly understood and its characterization is of significant interest, potentially offering interventional opportunities in relation to synthetic lethal behaviours in arrest-defective tumours. Using the catalytic Topo2a inhibitor ICRF193, we have performed a genome-wide siRNA screen in arrest-competent, non-transformed cells, to identify genes essential for this arrest mechanism. In addition, we have counter-screened several DNA-damaging agents and demonstrate that the Topo2a-dependent arrest is genetically distinct from DNA damage checkpoints. We identify the components of the SMC5/6 complex, including the activity of the E3 SUMO ligase NSE2, as non-redundant players that control the timing of the Topo2a-dependent arrest in G2. We have independently verified the NSE2 requirement in fibroblasts from patients with germline mutations that cause severely reduced levels of NSE2. Through imaging Topo2a-dependent G2 arrested cells, an increased interaction between Topo2a and NSE2 is observed at PML bodies, which are known SUMOylation hotspots. We demonstrate that Topo2a is SUMOylated in an ICRF193-dependent manner by NSE2 at a novel non-canonical site (K1520) and that K1520 sumoylation is required for chromosome segregation but not the G2 arrest.

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“…In contrast, the third SMC family member, the SMC5/6 complex, is highly conserved in evolution, but its role is much less well defined (Arago ´n, 2018;Fernandez-Capetillo, 2016).…”

Section: Introductionmentioning

confidence: 99%

Inducible Degradation of the Human SMC5/6 Complex Reveals an Essential Role Only during Interphase

et al. 2020

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The (elusive) role of the SMC5/6 complex

Cited by 7 publications

References 7 publications

Arabidopsis NSE4 Proteins Act in Somatic Nuclei and Meiosis to Ensure Plant Viability and Fertility

Arabidopsis NSE4 Proteins Act in Somatic Nuclei and Meiosis to Ensure Plant Viability and Fertility

A genome-wide RNAi screen identifies the SMC5/6 complex as a non-redundant regulator of a Topo2a-dependent G2 arrest

Inducible Degradation of the Human SMC5/6 Complex Reveals an Essential Role Only during Interphase

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