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Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis

2016-10-01Journal article Open access
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dc.contributor.authorMartin, C.
dc.contributor.authorMurray, J.
dc.contributor.authorCarroll, P.
dc.contributor.authorLeitch, A.
dc.contributor.authorMackenzie, K.
dc.contributor.authorHalachev, M.
dc.contributor.authorFetit, A.
dc.contributor.authorKeith, C.
dc.contributor.authorBicknell, L.
dc.contributor.authorFluteau, A.
dc.contributor.authorGautier, P.
dc.contributor.authorHall, E.
dc.contributor.authorJoss, S.
dc.contributor.authorSoares, G.
dc.contributor.authorSilva, J.
dc.contributor.authorBober, M.
dc.contributor.authorDuker, A.
dc.contributor.authorWise, C.
dc.contributor.authorQuigley, A.
dc.contributor.authorPhadke, S.
dc.contributor.authorWood, A.
dc.contributor.authorVagnarelli, P.
dc.contributor.authorJackson, A.
dc.date.accessioned2017-06-26T16:06:46Z
dc.date.available2017-06-26T16:06:46Z
dc.date.issued2016-10-01
dc.description.abstractCompaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish "condensinopathies" as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGenes Dev. 2016 Oct 1;30(19):2158-2172pt_PT
dc.identifier.doi10.1101/gad.286351.116pt_PT
dc.identifier.issn0890-9369
dc.identifier.issn1549-5477
dc.identifier.urihttp://hdl.handle.net/10400.16/2129
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherCold Spring Harbor Laboratory Presspt_PT
dc.relation.publisherversionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088565/pdf/2158.pdfpt_PT
dc.subjectcondensinpt_PT
dc.subjectmicrocephalypt_PT
dc.subjectneurodevelopmentpt_PT
dc.subjectdecatenationpt_PT
dc.titleMutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceUnited States of Americapt_PT
oaire.citation.endPage2172pt_PT
oaire.citation.issue19pt_PT
oaire.citation.startPage2158pt_PT
oaire.citation.titleGenes and Developmentpt_PT
oaire.citation.volume30pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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