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

Simple item page
dc.citation.articleNumbere73348
dc.citation.journalTitleeLife
dc.citation.volumeNumber10
dc.contributor.authorHoulard, Martin
dc.contributor.authorCutts, Erin E.
dc.contributor.authorShamim, Muhammad S.
dc.contributor.authorGodwin, Jonathan
dc.contributor.authorWeisz, David
dc.contributor.authorPresser Aiden, Aviva
dc.contributor.authorAiden, Erez Lieberman
dc.contributor.authorSchermelleh, Lothar
dc.contributor.authorVannini, Alessandro
dc.contributor.authorNasmyth, Kim
dc.contributor.orgCenter for Theoretical Biological Physics
dc.date.accessioned2022-01-21T16:24:03Z
dc.date.available2022-01-21T16:24:03Z
dc.date.issued2021
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.
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.
dc.identifier.digitalelife-73348-v2
dc.identifier.doihttps://doi.org/10.7554/eLife.73348
dc.identifier.urihttps://hdl.handle.net/1911/111935
dc.language.isoeng
dc.publishereLife Sciences Publications Ltd
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.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleMCPH1 inhibits Condensin II during interphase by regulating its SMC2-Kleisin interface
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
elife-73348-v2.pdf
Size:
20.35 MB
Format:
Adobe Portable Document Format
Download
Collections
Faculty Publications