Epigenetic Inactivation and Subsequent Heterochromatinization of a Centromere Stabilize Dicentric Chromosomes

Sato, Hiroshi; Masuda, Fumie; Takayama, Yuko; Takahashi, Kohske; Saitoh, Shigeaki

doi:10.1016/j.cub.2012.02.062

Cited by 59 publications

(80 citation statements)

References 42 publications

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“…In fission yeast, Sato et al (136) have demonstrated that epigenetic inactivation is initiated by disassembly of kinetochore components. Mutations that compromise kinetochore protein promote centromere inactivation.…”

Section: Introductionmentioning

confidence: 99%

Centromeric Heterochromatin: The Primordial Segregation Machine

Bloom

2014

Annu. Rev. Genet.

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Centromeres are specialized domains of heterochromatin that provide the foundation for the kinetochore. Centromeric heterochromatin is characterized by specific histone modifications, a centromere-specific histone H3 variant (CENP-A), and the enrichment of cohesin, condensin, and topo-isomerase II. Centromere DNA varies orders of magnitude in size from 125 bp (budding yeast) to several megabases (human). In metaphase, sister kinetochores on the surface of replicated chromosomes face away from each other, where they establish microtubule attachment and bi-orientation. Despite the disparity in centromere size, the distance between separated sister kinetochores is remarkably conserved (approximately 1 μm) throughout phylogeny. The centromere functions as a molecular spring that resists microtubule-based extensional forces in mitosis. This review explores the physical properties of DNA in order to understand how the molecular spring is built and how it contributes to the fidelity of chromosome segregation.

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Section: Introductionmentioning

confidence: 99%

Centromeric Heterochromatin: The Primordial Segregation Machine

Bloom

2014

Annu. Rev. Genet.

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“…Another illustration of epigenetic regulation in S. pombe is provided by the way that cells deal with dicentric chromosomes. One centromere in a dicentric chromosome can become inactivated because of disassembly of the kinetochore and the CENP-A chromatin and assembly of heterochromatin over the central domain (Sato et al 2012). Even in the absence of heterochromatin components, centromeric shutdown can occur by the assembly of a hypoacetylated chromatin state.…”

Section: Epigenetic Inheritance Of the Functional Centromere Statementioning

confidence: 99%

Epigenetic Regulation of Chromatin States inSchizosaccharomyces pombe

Allshire

Ekwall

2015

Cold Spring Harb Perspect Biol

173

191

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SUMMARYThis article discusses the advances made in epigenetic research using the model organism fission yeast Schizosaccharomyces pombe. S. pombe has been used for epigenetic research since the discovery of position effect variegation (PEV). This is a phenomenon in which a transgene inserted within heterochromatin is variably expressed, but can be stably inherited in subsequent cell generations. PEV occurs at centromeres, telomeres, ribosomal DNA (rDNA) loci, and mating-type regions of S. pombe chromosomes. Heterochromatin assembly in these regions requires enzymes that modify histones and the RNA interference (RNAi) machinery. One of the key histone-modifying enzymes is the lysine methyltransferase Clr4, which methylates histone H3 on lysine 9 (H3K9), a classic hallmark of heterochromatin. The kinetochore is assembled on specialized chromatin in which histone H3 is replaced by the variant CENP-A. Studies in fission yeast have contributed to our understanding of the establishment and maintenance of CENP-A chromatin and the epigenetic activation and inactivation of centromeres.Outline

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“…One is centromere inactivation through DNA rearrangements or epigenetic switches at one centromere (Lejeune et al 1973;Avarello et al 1992;Kramer et al 1994;Pennaneach and Kolodner 2009;Mackinnon and Campbell 2011;Sato et al 2012;Song et al 2013). The other is telomere addition at the broken ends; for instance, by telomerase or break-induced replication (Murnane and Sabatier 2004;Pennaneach and Kolodner 2009).…”

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confidence: 99%

Cytokinesis breaks dicentric chromosomes preferentially at pericentromeric regions and telomere fusions

et al. 2015

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Dicentric chromosomes are unstable products of erroneous DNA repair events that can lead to further genome rearrangements and extended gene copy number variations. During mitosis, they form anaphase bridges, resulting in chromosome breakage by an unknown mechanism. In budding yeast, dicentrics generated by telomere fusion break at the fusion, a process that restores the parental karyotype and protects cells from rare accidental telomere fusion. Here, we observed that dicentrics lacking telomere fusion preferentially break within a 25-to 30-kb-long region next to the centromeres. In all cases, dicentric breakage requires anaphase exit, ruling out stretching by the elongated mitotic spindle as the cause of breakage. Instead, breakage requires cytokinesis. In the presence of dicentrics, the cytokinetic septa pinch the nucleus, suggesting that dicentrics are severed after actomyosin ring contraction. At this time, centromeres and spindle pole bodies relocate to the bud neck, explaining how cytokinesis can sever dicentrics near centromeres.

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Epigenetic Inactivation and Subsequent Heterochromatinization of a Centromere Stabilize Dicentric Chromosomes

Cited by 59 publications

References 42 publications

Centromeric Heterochromatin: The Primordial Segregation Machine

Centromeric Heterochromatin: The Primordial Segregation Machine

Epigenetic Regulation of Chromatin States inSchizosaccharomyces pombe

Cytokinesis breaks dicentric chromosomes preferentially at pericentromeric regions and telomere fusions

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