Chromosome Dynamics during Mitosis

Hirano, Takeshi

doi:10.1101/cshperspect.a015792

Cited by 54 publications

(53 citation statements)

References 101 publications

(102 reference statements)

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“…Shugoshin‐1 (Sgo1) protects cohesin proteins and centrosome integrity (Salic, Waters, & Mitchison, 2004; Schöckel, Möckel, Mayer, Boos, & Stemmann, 2011). Cohesins keep sister chromatids from prematurely separating during mitosis, thus ensuring mitotic fidelity (Hirano, 2015). The Sgo1 haploinsufficient (∓) mouse is a model of cohesinopathy and chromosome instability (CIN) (Rao et al., 2016; Wang et al., 2008; Yamada et al., 2012, 2015, 2016).…”

Section: Introductionmentioning

confidence: 99%

Spontaneous development of Alzheimer's disease‐associated brain pathology in a Shugoshin‐1 mouse cohesinopathy model

et al. 2018

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SummarySpontaneous late‐onset Alzheimer's disease (LOAD) accounts for more than 95% of all human AD. As mice do not normally develop AD and as understanding on molecular processes leading to spontaneous LOAD has been insufficient to successfully model LOAD in mouse, no mouse model for LOAD has been available. Existing mouse AD models are all early‐onset AD (EOAD) models that rely on forcible expression of AD‐associated protein(s), which may not recapitulate prerequisites for spontaneous LOAD. This limitation in AD modeling may contribute to the high failure rate of AD drugs in clinical trials. In this study, we hypothesized that genomic instability facilitates development of LOAD and tested two genomic instability mice models in the brain pathology at the old age. Shugoshin‐1 (Sgo1) haploinsufficient (∓) mice, a model of chromosome instability (CIN) with chromosomal and centrosomal cohesinopathy, spontaneously exhibited a major feature of AD pathology; amyloid beta accumulation that colocalized with phosphorylated Tau, beta‐secretase 1 (BACE), and mitotic marker phospho‐Histone H3 (p‐H3) in the brain. Another CIN model, spindle checkpoint‐defective BubR1−/+ haploinsufficient mice, did not exhibit the pathology at the same age, suggesting the prolonged mitosis‐origin of the AD pathology. RNA‐seq identified ten differentially expressed genes, among which seven genes have indicated association with AD pathology or neuronal functions (e.g., ARC, EBF3). Thus, the model represents a novel model that recapitulates spontaneous LOAD pathology in mouse. The Sgo1−/+ mouse may serve as a novel tool for investigating mechanisms of spontaneous progression of LOAD pathology, for early diagnosis markers, and for drug development.

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Section: Introductionmentioning

confidence: 99%

Spontaneous development of Alzheimer's disease‐associated brain pathology in a Shugoshin‐1 mouse cohesinopathy model

et al. 2018

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“…Meiosis-specific cohesin components, including SMC1β, two α-kleisins (REC8 and RAD21L) and a stromal antigen protein (STAG3), are important for these additional requirements of cohesins during meiosis (Bannister et al, 2004;Fukuda et al, 2014;Herrán et al, 2011;Hopkins et al, 2014;Llano et al, 2014;Revenkova et al, 2004;Winters et al, 2014;Xu et al, 2005). Mutation of meiosisspecific cohesin components in female mice results in an increased frequency of oocyte aneuploidy and premature ovarian failure The two condensin complexes (I and II) are composed of the SMC2 and SMC4 heterodimers, but their kleisin subunit and pair of HEAT repeat elements are unique (Hirano, 2015). Condensins localize to the longitudinal axes of bivalents following meiotic resumption in mouse oocytes, and both complexes are required for chromosome compaction before meiosis I (Houlard et al, 2015;Lee et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

SMC5/6 is required for the formation of segregation-competent bivalent chromosomes during meiosis I in mouse oocytes

et al. 2017

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SMC complexes include three major classes: cohesin, condensin and SMC5/6. However, the localization pattern and genetic requirements for the SMC5/6 complex during mammalian oogenesis have not previously been examined. In mouse oocytes, the SMC5/6 complex is enriched at the pericentromeric heterochromatin, and also localizes along chromosome arms during meiosis. The infertility phenotypes of females with a Zp3-Cre-driven conditional knockout (cKO) of Smc5 demonstrated that maternally expressed SMC5 protein is essential for early embryogenesis. Interestingly, protein levels of SMC5/6 complex components in oocytes decline as wild-type females age. When SMC5/6 complexes were completely absent in oocytes during meiotic resumption, homologous chromosomes failed to segregate accurately during meiosis I. Despite what appears to be an inability to resolve concatenation between chromosomes during meiosis, localization of topoisomerase IIα to bivalents was not affected; however, localization of condensin along the chromosome axes was perturbed. Taken together, these data demonstrate that the SMC5/6 complex is essential for the formation of segregation-competent bivalents during meiosis I, and findings suggest that age-dependent depletion of the SMC5/6 complex in oocytes could contribute to increased incidence of oocyte aneuploidy and spontaneous abortion in aging females.

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“…In parallel to this, the cohesin complex is deposited along the chromosomes to encircle and hold the sister chromatids together (Tanaka et al 2001;Nasmyth 2011). Most of the DNA catenanes are removed by topoisomerase IIα (TopIIα); either during S phase or during early mitosis when DNA condensation occurs (Hirano 2015). In the prophase of mitosis, most of the cohesin located on chromosome arms (but not at centromeres) is released in a condensation-dependent manner (Hirano 2015).…”

Section: The Origins Of Ufbsmentioning

confidence: 99%

Knotty Problems during Mitosis: Mechanistic Insight into the Processing of Ultrafine DNA Bridges in Anaphase

Sarlós

Biebricher

Petermann

et al. 2017

Cold Spring Harb Symp Quant Biol

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To survive and proliferate, cells have to faithfully segregate their newly replicated genomic DNA to the two daughter cells. However, the sister chromatids of mitotic chromosomes are frequently interlinked by so-called ultrafine DNA bridges (UFBs) that are visible in the anaphase of mitosis. UFBs can only be detected by the proteins bound to them and not by staining with conventional DNA dyes. These DNA bridges are presumed to represent entangled sister chromatids and hence pose a threat to faithful segregation. A failure to accurately unlink UFB DNA results in chromosome segregation errors and binucleation. This, in turn, compromises genome integrity, which is a hallmark of cancer. UFBs are actively removed during anaphase, and most known UFB-associated proteins are enzymes involved in DNA repair in interphase. However, little is known about the mitotic activities of these enzymes or the exact DNA structures present on UFBs. We focus on the biology of UFBs, with special emphasis on their underlying DNA structure and the decatenation machineries that process UFBs.

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Chromosome Dynamics during Mitosis

Cited by 54 publications

References 101 publications

Spontaneous development of Alzheimer's disease‐associated brain pathology in a Shugoshin‐1 mouse cohesinopathy model

Spontaneous development of Alzheimer's disease‐associated brain pathology in a Shugoshin‐1 mouse cohesinopathy model

SMC5/6 is required for the formation of segregation-competent bivalent chromosomes during meiosis I in mouse oocytes

Knotty Problems during Mitosis: Mechanistic Insight into the Processing of Ultrafine DNA Bridges in Anaphase

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