Dataset Information

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

ABSTRACT: Compaction 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.

SUBMITTER: Martin CA

PROVIDER: S-EPMC5088565 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Martin Carol-Anne CA Murray Jennie E JE Carroll Paula P Leitch Andrea A Mackenzie Karen J KJ Halachev Mihail M Fetit Ahmed E AE Keith Charlotte C Bicknell Louise S LS Fluteau Adeline A Gautier Philippe P Hall Emma A EA Joss Shelagh S Soares Gabriela G Silva João J Bober Michael B MB Duker Angela A Wise Carol A CA Quigley Alan J AJ Phadke Shubha R SR Wood Andrew J AJ Vagnarelli Paola P Jackson Andrew P AP

Genes & development 20161013 19

Compaction 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 ...[more]

PMID: 27737959

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Similar Datasets

Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy.
| S-EPMC4676084 | biostudies-literature

Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome.
| S-EPMC4000253 | biostudies-literature

Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly.
| S-EPMC2668020 | biostudies-literature

Mutations in PYCR2, Encoding Pyrroline-5-Carboxylate Reductase 2, Cause Microcephaly and Hypomyelination.
| S-EPMC4570282 | biostudies-literature

PYCR2 Mutations cause a lethal syndrome of microcephaly and failure to thrive.
| S-EPMC4938747 | biostudies-literature

Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly.
| S-EPMC5819591 | biostudies-literature

Condensin aids sister chromatid decatenation by topoisomerase II.
| S-EPMC3874195 | biostudies-literature

Mutations in QARS, encoding glutaminyl-tRNA synthetase, cause progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures.
| S-EPMC3980424 | biostudies-literature

Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture.
| S-EPMC2969850 | biostudies-literature

Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.
| S-EPMC7251970 | biostudies-literature