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

Fabien Abdul, Aurélie Diman, Bastien Baechler, Dhivya Ramakrishnan, Dmytro Kornyeyev, Rudolf K Beran, Simon P Fletcher, Michel Strubin

Nature structural & molecular biology 2022 Sep

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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. © 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.

Citation

Fabien Abdul, Aurélie Diman, Bastien Baechler, Dhivya Ramakrishnan, Dmytro Kornyeyev, Rudolf K Beran, Simon P Fletcher, Michel Strubin. Smc5/6 silences episomal transcription by a three-step function. Nature structural & molecular biology. 2022 Sep;29(9):922-931