Scientific article
Open access

Smc5/6 silences episomal transcription by a three-step function

Publication date2022-09-12
First online date2022-09-12

In addition to its role in chromosome maintenance, the six-membered Smc5/6 complex functions as a restriction factor that binds to and transcriptionally silences viral and other episomal DNA. However, the underlying mechanism is unknown. Here, we show that transcriptional silencing by the human Smc5/6 complex is a three-step process. The first step is entrapment of the episomal DNA by a mechanism dependent on Smc5/6 ATPase activity and a function of its Nse4a subunit for which the Nse4b paralog cannot substitute. The second step results in Smc5/6 recruitment to promyelocytic leukemia nuclear bodies by SLF2 (the human ortholog of Nse6). The third step promotes silencing through a mechanism requiring Nse2 but not its SUMO ligase activity. By contrast, the related cohesin and condensin complexes fail to bind to or silence episomal DNA, indicating a property unique to Smc5/6.

  • Virus
  • Host-pathogen interaction
  • HBV
  • Restriction factors
  • Episomal DNA
  • Extrachromosomal DNA
  • Molecular biology
  • Silencing
  • Restriction
  • Smc56
Citation (ISO format)
ABDUL, Fabien et al. Smc5/6 silences episomal transcription by a three-step function. In: Nature structural & molecular biology, 2022. doi: 10.1038/s41594-022-00829-0
Main files (2)
Article (Published version)
Article (Accepted version)
ISSN of the journal1545-9985

Technical informations

Creation09/13/2022 1:19:00 PM
First validation09/13/2022 1:19:00 PM
Update time03/16/2023 7:33:47 AM
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