The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis

Westhorpe, Frederick G.; Straight, Aaron F.

doi:10.1101/cshperspect.a015818

Cited by 149 publications

(86 citation statements)

References 163 publications

(230 reference statements)

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“…Centromere-associated proteins are functionally conserved among eukaryote species (1)(2)(3). Nearly all eukaryotes studied to date possess a version of a specialized centromeric histone protein (CENH3, also described as centromere protein A, CENP-A), which binds to centromeric DNA and replaces the histone H3 at the site of kinetochore assembly (4)(5)(6). Conversely, the centromeric DNA sequences themselves are extremely variable and appear to evolve rapidly, even among similar organisms (7).…”

mentioning

confidence: 99%

Diatom centromeres suggest a mechanism for nuclear DNA acquisition

Diner

Noddings

Lian

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Centromeres are essential for cell division and growth in all eukaryotes, and knowledge of their sequence and structure guides the development of artificial chromosomes for functional cellular biology studies. Centromeric proteins are conserved among eukaryotes; however, centromeric DNA sequences are highly variable. We combined forward and reverse genetic approaches with chromatin immunoprecipitation to identify centromeres of the model diatom Phaeodactylum tricornutum. We observed 25 unique centromere sequences typically occurring once per chromosome, a finding that helps to resolve nuclear genome organization and indicates monocentric regional centromeres. Diatom centromere sequences contain low-GC content regions but lack repeats or other conserved sequence features. Native and foreign sequences with similar GC content to P. tricornutum centromeres can maintain episomes and recruit the diatom centromeric histone protein CENH3, suggesting nonnative sequences can also function as diatom centromeres. Thus, simple sequence requirements may enable DNA from foreign sources to persist in the nucleus as extrachromosomal episomes, revealing a potential mechanism for organellar and foreign DNA acquisition.diatom | Phaeodactylum tricornutum | episome | centromere | CENH3

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mentioning

confidence: 99%

Diatom centromeres suggest a mechanism for nuclear DNA acquisition

Diner

Noddings

Lian

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Moreover, several species including some kinetoplastids (Akiyoshi and Gull 2014;Berriman et al 2005) and holocentric insects (Drinnenberg et al 2014) have lost the centromere-specific histone H3 gene. This loss is even more surprising given that Cenp-A and the orthologous proteins of other species are assembled into centromere-specific nucleosomes that appear to function as epigenetic centromere mark (Fachinetti et al 2013;Guse et al 2011;Hori et al 2013;Mendiburo et al 2011;Westhorpe and Straight 2015). In addition, Cenp-A starts a recruitment cascade that allows assembly of kinetochore proteins at the start of M phase.…”

Section: Introductionmentioning

confidence: 99%

Drosophila Nnf1 paralogs are partially redundant for somatic and germ line kinetochore function

et al. 2016

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Kinetochores allow attachment of chromosomes to spindle microtubules. Moreover, they host proteins that permit correction of erroneous attachments and prevent premature anaphase onset before bi-orientation of all chromosomes in metaphase has been achieved. Kinetochores are assembled from subcomplexes. Kinetochore proteins as well as the underlying centromere proteins and the centromeric DNA sequences evolve rapidly despite their fundamental importance for faithful chromosome segregation during mitotic and meiotic divisions. During evolution of Drosophila melanogaster, several centromere proteins were lost and a recent gene duplication has resulted in two Nnf1 paralogs, Nnf1a and Nnf1b, which code for alternative forms of a Mis12 kinetochore complex component. The rapid evolutionary divergence of centromere/kinetochore constituents in animals and plants has been proposed to be driven by an intragenome conflict resulting from centromere drive during female meiosis. Thus, a female meiosisspecific paralog might be expected to evolve rapidly under positive selection. While our characterization of the D. melanogaster Nnf1 paralogs hints at some partial functional specialization of Nnf1b for meiosis, we have failed to detect evidence for positive selection in our analysis of Nnf1 sequence evolution in the Drosophilid lineage. Neither paralog is essential, even though we find some clear differences in subcellular localization and expression during development. Loss of both paralogs results in developmental lethality. We therefore conclude that the two paralogs are still in early stages of differentiation. Neither paralog is essential, even though we find some clear differences in subcellular localization and expression during development. Loss of both paralogs results in developmental lethality. We therefore conclude that the two paralogs are still in early stages of differentiation.

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“…CCAN, a complex of more than a dozen conserved proteins, forms the inner kinetochore, which associates with centromeric chromatin (McAinsh and Meraldi 2011;Westhorpe and Straight 2015). An outer kinetochore network, named KMN for its three major constituents, Knl1, the Mis12 (or MIND) complex, and the Ndc80 complex, mediates the association of the CCAN with spindle microtubules (Cheeseman et al 2006;Santaguida and Musacchio 2009;Foley and Kapoor 2013).…”

Section: Msc1 May Function In Localizing Hdac Activity To Centromeresmentioning

confidence: 99%

“…The constitutive centromere-associated network (CCAN) forms the inner kinetochore and consists of more than a dozen conserved proteins, including fission yeast Mis6 (CENP-I in mammalian cells) that promotes incorporation of CENP-A at the centromere (McAinsh and Meraldi 2011;Westhorpe and Straight 2015). The KMN network is composed of the tethering protein Knl1, the Mis12 complex, and the NDC80 complex, a heterotetramer consisting of Ndc80, Nuf2, Spc24, and Spc25, that links microtubules to the kinetochore (Petrovic et al 2014).…”

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confidence: 99%

Escape from Mitotic Arrest: An Unexpected Connection Between Microtubule Dynamics and Epigenetic Regulation of Centromeric Chromatin in Schizosaccharomyces pombe

George

Walworth

2015

Genetics

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Accurate chromosome segregation is necessary to ensure genomic integrity. Segregation depends on the proper functioning of the centromere, kinetochore, and mitotic spindle microtubules and is monitored by the spindle assembly checkpoint (SAC). In the fission yeast Schizosaccharomyces pombe, defects in Dis1, a microtubule-associated protein that influences microtubule dynamics, lead to mitotic arrest as a result of an active SAC and consequent failure to grow at low temperature. In a mutant dis1 background (dis1-288), loss of function of Msc1, a fission yeast homolog of the KDM5 family of proteins, suppresses the growth defect and promotes normal mitosis. Genetic analysis implicates a histone deacetylase (HDAC)-linked pathway in suppression because HDAC mutants clr6-1, clr3D, and sir2D, though not hos2D, also promote normal mitosis in the dis1-288 mutant. Suppression of the dis phenotype through loss of msc1 function requires the spindle checkpoint protein Mad2 and is limited by the presence of the heterochromatin-associated HP1 protein homolog Swi6. We speculate that alterations in histone acetylation promote a centromeric chromatin environment that compensates for compromised dis1 function by allowing for successful kinetochore-microtubule interactions that can satisfy the SAC. In cells arrested in mitosis by mutation of dis1, loss of function of epigenetic determinants such as Msc1 or specific HDACs can promote cell survival. Because the KDM5 family of proteins has been implicated in human cancers, an appreciation of the potential role of this family of proteins in chromosome segregation is warranted. KEYWORDS Msc1; lysine demethylase KDM5; histone deacetylase (HDAC); Rb; PLU-1; RBP2; trichostatin; thiabendazole; Mad2; Dis1 (XMAP215, TOG1); Swi6 (HP1 homolog) A CCURATE chromosome segregation relies on precise assembly of the multiprotein kinetochore complex, which mediates the link between chromosomes and the mitotic spindle (Przewloka and Glover 2009). The histone H3 variant CENP-A, along with epigenetic marks on canonical histones, defines centromeric chromatin, which forms the template for kinetochore assembly (Allshire and Karpen 2008;Verdaasdonk and Bloom 2011). Kinetochores serve as the site of spindle microtubule attachment (Santaguida and Musacchio 2009) and, along with the centromere, translate microtubule attachment status to mediate force balance, tension sensing, and spindle checkpoint control (Bloom 2014). When associations between chromosomes and the spindle are incorrect, the spindle assembly checkpoint (SAC) delays progression through mitosis by preventing the onset of anaphase (Musacchio and Salmon 2007;Foley and Kapoor 2013).Fission yeast centromeric chromatin (Allshire and Ekwall 2015) consists of a central core (cnt) and internal inverted repeats (imr), defined by the presence of CENP-A and methylated histone H3 K4 chromatin, flanked by heterochromatic outer repeats (otr) marked by methylated histone H3 K9 (Partridge et al. 2000;Takahashi et al. 2000;Kniola et al. 2001). The consti...

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The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis

Cited by 149 publications

References 163 publications

Diatom centromeres suggest a mechanism for nuclear DNA acquisition

Diatom centromeres suggest a mechanism for nuclear DNA acquisition

Drosophila Nnf1 paralogs are partially redundant for somatic and germ line kinetochore function

Escape from Mitotic Arrest: An Unexpected Connection Between Microtubule Dynamics and Epigenetic Regulation of Centromeric Chromatin in Schizosaccharomyces pombe

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