Hit the brakes - A new perspective on the loop extrusion mechanism of cohesin and other SMC complexes

Avi Matityahu, Itay Onn

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The three-dimensional structure of chromatin is determined by the action of protein complexes of the structural maintenance of chromosome (SMC) family. Eukaryotic cells contain three SMC complexes, cohesin, condensin, and a complex of Smc5 and Smc6. Initially, cohesin was linked to sister chromatid cohesion, the process that ensures the fidelity of chromosome segregation in mitosis. In recent years, a second function in the organization of interphase chromatin into topologically associated domains has been determined, and loop extrusion has emerged as the leading mechanism of this process. Interestingly, fundamental mechanistic differences exist between mitotic tethering and loop extrusion. As distinct molecular switches that aim to suppress loop extrusion in different biological contexts have been identified, we hypothesize here that loop extrusion is the default biochemical activity of cohesin and that its suppression shifts cohesin into a tethering mode.With this model, we aim to provide an explanation for how loop extrusion and tethering can coexist in a single cohesin complex and also apply it to the other eukaryotic SMC complexes, describing both similarities and differences between them. Finally, we present model-derived molecular predictions that can be tested experimentally, thus offering a new perspective on the mechanisms by which SMC complexes shape the higher-order structure of chromatin.

Original languageEnglish
Article numberjcs247577
JournalJournal of Cell Science
Volume134
Issue number1
DOIs
StatePublished - 8 Jan 2021

Bibliographical note

Publisher Copyright:
© 2021 Company of Biologists Ltd. All rights reserved.

Funding

The work of the Onn laboratory is supported by Israel Science Foundation grant 987/20 (I.O.).

FundersFunder number
Israel Science Foundation987/20

    Keywords

    • Cohesin
    • Condensin
    • Loop extrusion
    • SMC complex
    • Sister chromatid cohesion
    • Smc5/6

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