DNA Recruitment, Regulation & Function of SMC5/6

• Applicant: Dr. Markus Räschle
• Subject Area: Cell Biology
• Term: from 2016 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 323666480

• Final Report Year: 2021

Final Report Abstract

In summary our study shows the potential of the egg extracts system for investigating SMC5/6 function, but clearly more work is required to optimize SMC5/6 depletion and rescue conditions. Due to the inherent synchrony of replication and the possibility to use DNA templates with defined lesions it was possible to demonstrate both replication- and DNA damage-dependent chromatin recruitment of the SMC5/6 complex. With their ability to recapitulate complex replication-coupled DNA repair reactions and the possibility to follow chromosome segregation in a biochemically tractable system, xenopus egg extracts likely will play a key role in unlocking the enigmatic functions of the SMC5/6 complex.

Publications

• Replication Coupled DNA-Protein Crosslink Repair by SPRTN and the Proteasome in Xenopus Egg Extracts. Mol Cell, 2019. 73: p. 1-15
  Larsen, Nicolai B.; Gao, Alan O.; Sparks, Justin L.; Gallina, Irene; Wu, R. Alex; Mann, Matthias; Räschle, Markus; Walter, Johannes C. & Duxin, Julien P.
  
• The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair. Cell, 2019. 176(1-2): p. 167-181
  Sparks, Justin L.; Chistol, Gheorghe; Gao, Alan O.; Räschle, Markus; Larsen, Nicolai B.; Mann, Matthias; Duxin, Julien P. & Walter, Johannes C.
  
• NSE5/6 inhibits the SMC5/6 ATPase to facilitate DNA substrate selection. (2021)
  Taschner, Michael; Basquin, Jérôme; Steigenberger, Barbara; Schaefer, Ingmar; Soh, Young-Min; Basquin, Claire; Lorentzen, Esben; Räschle, Markus; Scheltema, Richard A. & Gruber, Stephan