Smc5/6 Silences Episomal Transcription by a Three-step Function

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2022 Sep 13

PMID 36097294

Authors

Fabien Abdul

Aurelie Diman

Bastien Baechler

Dhivya Ramakrishnan

Dmytro Kornyeyev

Rudolf K Beran

Simon P Fletcher

Michel Strubin

Affiliations

Soon will be listed here.

Abstract

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.

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