A family of Structural Maintenance of Chromosome (SMC) complexes is essential for key cellular processes ensuring proper cohesion, condensation and replication. They share a common SMC-kleisin architecture allowing them to embrace DNA. In SMC5/6, the NSE1 and NSE3 KITE and NSE4 kleisin subunits form a stable subcomplex that binds DNA and regulates essential processes. In addition, NSE5 and NSE6 subunits associate with the core SMC5/6 complex and recruit it to DNA repair sites. The architecture of the SMC5/6 complex is crucial for its proper functioning, and mutations within the human SMC5/6 subunits result in severe syndromes. Therefore, we aimed to analyze interactions within the human SMC5/6 complex and determine its detailed architecture. Firstly, we analyzed different parts of SMC5/6 by crosslinking and MS/MS analysis. Our data suggested domain arrangements of hNSE1-hNSE3 and orientation of hNSE4 within the hNSE1-hNSE3-hNSE4 subcomplex. The crosslinking and electron microscopic analysis of the SMC5/6 core complex showed its rod-like architecture with juxtaposed hSMC5-hSMC6 arms. Additionally, we observed fully or partially opened hSMC5-hSMC6 shapes with the hNSE1-hNSE3-hNSE4 trimer localized in the SMC head domains. To complete mapping of the human SMC5/6 complex architecture, we analyzed positions of hNSE5-hNSE6 at the hSMC5-hSMC6 arms. We showed that hNSE6 binding to hNSE5 and the coiled-coil arm of hSMC6 is mediated by a conserved FAM178 domain, which we therefore renamed CANIN (Coiled-coil SMC6 And NSE5 INteracting) domain. Interestingly, hNSE6 bound both hSMC5 and hSMC6 arms, suggesting that hNSE6 may lock the arms and regulate the dynamics of the human SMC5/6 complex.

• MeSH
• chromozomální proteiny, nehistonové genetika   MeSH
• lidé MeSH
• multimerizace proteinu genetika   MeSH
• multiproteinové komplexy genetika   MeSH
• mutace MeSH
• oprava DNA genetika   MeSH
• proteinové domény genetika   MeSH
• proteiny buněčného cyklu genetika   MeSH
• transportní proteiny genetika   MeSH
• vazba proteinů genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: In a previous study we compared rocuronium and suxamethonium for rapid-sequence induction of general anaesthesia for caesarean section and found no difference in maternal outcome. There was however, a significant difference in Apgar scores. As this was a secondary outcome, we extended the study to explore this finding on a larger sample. METHODS: We included 488 parturients of whom 240 were women from the original study. Women were randomly assigned to receive either rocuronium 1mg/kg (ROC n=245) or suxamethonium 1mg/kg (SUX n=243) after propofol 2mg/kg. Anaesthesia was maintained with up to 50% nitrous oxide and up to one minimum alveolar concentration of sevoflurane until the umbilical cord was clamped. We compared neonatal outcome using Apgar scores and umbilical cord blood gases. RESULTS: Data were analysed for 525 newborns (ROC n=263vs. SUX n=262). There was a statistically significant difference in the proportion of Apgar scores <7 at 1min (ROC 17.5% vs. SUX 10.3%, P=0.023) but no difference at 5min (ROC 8% vs. SUX 4.2%, P=0.1) or 10min (ROC 3.0% vs. SUX 1.9%, P=0.58). There was no difference between groups in other measured outcomes. CONCLUSION: The use of rocuronium was associated with lower Apgar scores at 1min compared with suxamethonium. The clinical significance of this is unclear and warrants further investigation.

• MeSH
• androstanoly farmakologie   MeSH
• Apgar skóre * MeSH
• celková anestezie metody   MeSH
• císařský řez MeSH
• dospělí MeSH
• lidé MeSH
• novorozenec MeSH
• porodnická anestezie metody   MeSH
• sukcinylcholin farmakologie   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH