MCPH1 inhibits Condensin II during interphase by regulating its SMC2-Kleisin interface

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dc.citation.articleNumbere73348en_US
dc.citation.journalTitleeLifeen_US
dc.citation.volumeNumber10en_US
dc.contributor.authorHoulard, Martinen_US
dc.contributor.authorCutts, Erin E.en_US
dc.contributor.authorShamim, Muhammad S.en_US
dc.contributor.authorGodwin, Jonathanen_US
dc.contributor.authorWeisz, Daviden_US
dc.contributor.authorPresser Aiden, Avivaen_US
dc.contributor.authorAiden, Erez Liebermanen_US
dc.contributor.authorSchermelleh, Lotharen_US
dc.contributor.authorVannini, Alessandroen_US
dc.contributor.authorNasmyth, Kimen_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2022-01-21T16:24:03Zen_US
dc.date.available2022-01-21T16:24:03Zen_US
dc.date.issued2021en_US
dc.description.abstractDramatic change in chromosomal DNA morphology between interphase and mitosis is a defining features of the eukaryotic cell cycle. Two types of enzymes, namely cohesin and condensin confer the topology of chromosomal DNA by extruding DNA loops. While condensin normally configures chromosomes exclusively during mitosis, cohesin does so during interphase. The processivity of cohesin’s loop extrusion during interphase is limited by a regulatory factor called WAPL, which induces cohesin to dissociate from chromosomes via a mechanism that requires dissociation of its kleisin from the neck of SMC3. We show here that a related mechanism may be responsible for blocking condensin II from acting during interphase. Cells derived from patients affected by microcephaly caused by mutations in the MCPH1 gene undergo premature chromosome condensation. We show that deletion of Mcph1 in mouse embryonic stem cells unleashes an activity of condensin II that triggers formation of compact chromosomes in G1 and G2 phases, accompanied by enhanced mixing of A and B chromatin compartments, and this occurs even in the absence of CDK1 activity. Crucially, inhibition of condensin II by MCPH1 depends on the binding of a short linear motif within MCPH1 to condensin II’s NCAPG2 subunit. MCPH1’s ability to block condensin II’s association with chromatin is abrogated by the fusion of SMC2 with NCAPH2, hence may work by a mechanism similar to cohesin. Remarkably, in the absence of both WAPL and MCPH1, cohesin and condensin II transform chromosomal DNAs of G2 cells into chromosomes with a solenoidal axis.en_US
dc.identifier.citationHoulard, Martin, Cutts, Erin E., Shamim, Muhammad S., et al.. "MCPH1 inhibits Condensin II during interphase by regulating its SMC2-Kleisin interface." <i>eLife,</i> 10, (2021) eLife Sciences Publications Ltd: https://doi.org/10.7554/eLife.73348.en_US
dc.identifier.digitalelife-73348-v2en_US
dc.identifier.doihttps://doi.org/10.7554/eLife.73348en_US
dc.identifier.urihttps://hdl.handle.net/1911/111935en_US
dc.language.isoengen_US
dc.publishereLife Sciences Publications Ltden_US
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleMCPH1 inhibits Condensin II during interphase by regulating its SMC2-Kleisin interfaceen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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