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Topoisomerases I and II facilitate condensin DC translocation to organize and repress X chromosomes in C. elegans.


ABSTRACT: Condensins are evolutionarily conserved molecular motors that translocate along DNA and form loops. To address how DNA topology affects condensin translocation, we applied auxin-inducible degradation of topoisomerases I and II and analyzed the binding and function of an interphase condensin that mediates X chromosome dosage compensation in C. elegans. TOP-2 depletion reduced long-range spreading of condensin-DC (dosage compensation) from its recruitment sites and shortened 3D DNA contacts measured by Hi-C. TOP-1 depletion did not affect long-range spreading but resulted in condensin-DC accumulation within expressed gene bodies. Both TOP-1 and TOP-2 depletion resulted in X chromosome derepression, indicating that condensin-DC translocation at both scales is required for its function. Together, the distinct effects of TOP-1 and TOP-2 suggest two distinct modes of condensin-DC association with chromatin: long-range DNA loop extrusion that requires decatenation/unknotting of DNA and short-range translocation across genes that requires resolution of transcription-induced supercoiling.

SUBMITTER: Morao AK 

PROVIDER: S-EPMC9837612 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Topoisomerases I and II facilitate condensin DC translocation to organize and repress X chromosomes in C. elegans.

Morao Ana Karina AK   Kim Jun J   Obaji Daniel D   Sun Siyu S   Ercan Sevinç S  

Molecular cell 20221026 22


Condensins are evolutionarily conserved molecular motors that translocate along DNA and form loops. To address how DNA topology affects condensin translocation, we applied auxin-inducible degradation of topoisomerases I and II and analyzed the binding and function of an interphase condensin that mediates X chromosome dosage compensation in C. elegans. TOP-2 depletion reduced long-range spreading of condensin-DC (dosage compensation) from its recruitment sites and shortened 3D DNA contacts measur  ...[more]

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