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 NB, Gao AO, Sparks JL, Gallina I, Wu RA, Mann M, Räschle M, Walter JC, Duxin JP
  (See online at https://doi.org/10.1016/j.molcel.2018.11.024)
• The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair. Cell, 2019. 176(1-2): p. 167-181
  Sparks JL, Christol G, Gao AO, Räschle M, Larsen NB, Mann M, Duxin JP, Walter JC
  (See online at https://doi.org/10.1016/j.cell.2018.10.053)
• NSE5/6 inhibits the SMC5/6 ATPase to facilitate DNA substrate selection. (2021)
  Michael Taschner, Jérôme Basquin, Barbara Steigenberger, Ingmar Schaefer, Young-Min Soh, Claire Basquin, Esben Lorentzen, Markus Räschle, Richard A. Scheltema, Stephan Gruber
  (See online at https://doi.org/10.1101/2021.02.09.430422)