SMC1 involvement in fragile site expression

Musio, Antonio; Montagna, Cristina; Mariani, Tullio; Tilenni, Manuela; Focarelli, Maria Luisa; Brait, Lorenzo; Indino, Esterina; Benedetti, Pier Alberto; Chessa, Luciana; Albertini, Alberto; Ried, Thomas; Vezzoni, Paolo

doi:10.1093/hmg/ddi049

Cited by 86 publications

(76 citation statements)

References 41 publications

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“…Key roles for cohesin have been shown in a number of cellular processes including DNA repair, 21,22 chromatin modification, 23 DNA condensation 24 and transcriptional regulation in Drosophila, [25][26][27][28] [36][37][38] have demonstrated that the function of Scc2/NIPBL in sister chromatid cohesion is spatially and temporally associated with that of Scc4/MAU2. The C. elegans homolog mau-2 was originally identified for its role in axon guidance 39 and has subsequently been show to have a role in mitotic chromosome segregation.…”

Section: Cdlsmentioning

confidence: 99%

Isolated NIBPL missense mutations that cause Cornelia de Lange syndrome alter MAU2 interaction

et al. 2011

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Cornelia de Lange syndrome (CdLS; or Brachmann-de Lange syndrome) is a dominantly inherited congenital malformation disorder with features that include characteristic facies, cognitive delays, growth retardation and limb anomalies. Mutations in nearly 60% of CdLS patients have been identified in NIPBL, which encodes a regulator of the sister chromatid cohesion complex. NIPBL, also known as delangin, is a homolog of yeast and amphibian Scc2 and C. elegans PQN-85. Although the exact mechanism of NIPBL function in sister chromatid cohesion is unclear, in vivo yeast and C. elegans experiments and in vitro vertebrate cell experiments have demonstrated that NIPBL/Scc2 functionally interacts with the MAU2/Scc4 protein to initiate loading of cohesin onto chromatin. To test the significance of this model in the clinical setting of CdLS, we fine-mapped the NIPBL-MAU2 interaction domain and tested the functional significance of missense mutations and variants in NIPBL and MAU2 identified in these minimal domains in a cohort of patients with CdLS. We demonstrate that specific novel mutations at the N-terminus of the MAU2-interacting domain of NIPBL result in markedly reduced MAU2 binding, although we appreciate no consistent clinical difference in the small group of patients with these mutations. These data suggest that factors in addition to MAU2 are essential in determining the clinical features and severity of CdLS.

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Section: Cdlsmentioning

confidence: 99%

Isolated NIBPL missense mutations that cause Cornelia de Lange syndrome alter MAU2 interaction

et al. 2011

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“…In a yeast model system for studying CFSs, CFS breakage has been shown to depend on condensin and topoisomerase II (Hashash et al 2012). Conversely, an early study implicated the role of cohesin in suppressing CFS breakage in human cells (Musio et al 2005).…”

Section: Mitotic Chromosome Dynamicsmentioning

confidence: 99%

Chromosome Dynamics during Mitosis

Hirano

2015

Cold Spring Harb Perspect Biol

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The primary goal of mitosis is to partition duplicated chromosomes into daughter cells. Eukaryotic chromosomes are equipped with two distinct classes of intrinsic machineries, cohesin and condensins, that ensure their faithful segregation during mitosis. Cohesin holds sister chromatids together immediately after their synthesis during S phase until the establishment of bipolar attachments to the mitotic spindle in metaphase. Condensins, on the other hand, attempt to "resolve" sister chromatids by counteracting cohesin. The products of the balancing acts of cohesin and condensins are metaphase chromosomes, in which two rod-shaped chromatids are connected primarily at the centromere. In anaphase, this connection is released by the action of separase that proteolytically cleaves the remaining population of cohesin. Recent studies uncover how this series of events might be mechanistically coupled with each other and intricately regulated by a number of regulatory factors.

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“…SMC1L1 (structural maintenance of chromosomes 1-like 1, or SMC1A; MIM #300040) maps to chromosome Xp11.22 and encodes one of the four cohesin subunits which hold sister chromatids together from S phase until the beginning of anaphase (Nasmyth and Haering, 2005). SMC1L1 has also been shown to be involved in genome stability and DNA repair (Musio et al, 2005;Watrin and Peters, 2006). The phenotype of X-linked CdLS (X-CdLS; MIM #300590) in the four reported males seemed to differ from the typical form by a milder dysmorphism, mild or no growth retardation and absence of microcephaly (Musio et al, 2006).…”

Section: Introductionmentioning

confidence: 99%