A 17-kD centromere protein (CENP-A) copurifies with nucleosome core particles and with histones

Palmer, Douglas K.; O'Day, Kathleen; Wener, Mark H.; Andrews, Brian S.; Margolis, Robert L.

doi:10.1083/jcb.104.4.805

Cited by 385 publications

(256 citation statements)

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“…One hallmark of all kinetochores is the essential CenH3 (Palmer et al, 1987;Stoler et al, 1995;Buchwitz et al, 1999;Henikoff et al, 2000;Takahashi et al, 2000;Sanyal and Carbon, 2002;Talbert et al, 2002;Zhong et al, 2002;Edwards and Murray, 2005). CenH3s contain a unique N terminus and a well-conserved C terminus that is highly homologous to histone H3 (Malik and Henikoff, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Outer kinetochore complexes include the conserved NDC80 (Ndc80, Spc24, Spc25, and Nuf2) and DAM1 (Dam1, Ask1, Duo1, Dad1, Dad2, Dad3, Dad4, Spc19, Spc34, and Hsk3) complexes. DAM1 is considered to be the outermost complex because it requires microtubules and all other complexes for kinetochore localization (Enquist-Newman et al, 2001;Janke et al, 2002;Li et al, 2002).One hallmark of all kinetochores is the essential CenH3 (Palmer et al, 1987;Stoler et al, 1995;Buchwitz et al, 1999;Henikoff et al, 2000;Takahashi et al, 2000;Sanyal and Carbon, 2002;Talbert et al, 2002;Zhong et al, 2002;Edwards and Murray, 2005). CenH3s contain a unique N terminus and a well-conserved C terminus that is highly homologous to histone H3 (Malik and Henikoff, 2003).…”

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confidence: 99%

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De Novo Kinetochore Assembly Requires the Centromeric Histone H3 Variant

Collins

Castillo

Tatsutani

et al. 2005

MBoC

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Kinetochores mediate chromosome attachment to the mitotic spindle to ensure accurate chromosome segregation. Budding yeast is an excellent organism for kinetochore assembly studies because it has a simple defined centromere sequence responsible for the localization of >65 proteins. In addition, yeast is the only organism where a conditional centromere is available to allow studies of de novo kinetochore assembly. Using a conditional centromere, we found that yeast kinetochore assembly is not temporally restricted and can occur in both G 1 phase and prometaphase. We performed the first investigation of kinetochore assembly in the absence of the centromeric histone H3 variant Cse4 and found that all proteins tested depend on Cse4 to localize. Consistent with this observation, Cse4-depleted cells had severe chromosome segregation defects. We therefore propose that yeast kinetochore assembly requires both centromeric DNA specificity and centromeric chromatin. INTRODUCTIONAccurate chromosome segregation in mitosis and meiosis is essential for the maintenance of genomic stability. Chromosomes attach to the mitotic spindle at the kinetochore, the protein complex that assembles onto centromeric DNA. Although kinetochore function is conserved, the underlying centromeric DNA is highly variable. Budding yeast contain a 125-base pair sequence-specific centromere that is sufficient for kinetochore formation (Fitzgerald-Hayes et al., 1982). In contrast, centromeres in multicellular eukaryotes are composed of megabases of highly repetitive DNA that lack sequence specificity (for review, see Sullivan et al., 2001). In these organisms, kinetochore assembly seems to be propagated by unidentified epigenetic component(s) (Karpen and Allshire, 1997;Sullivan et al., 2001).The best-characterized kinetochore is in budding yeast where Ͼ65 components have been identified that constitutively localize to the kinetochore (for reviews, see Biggins and Walczak, 2003;McAinsh et al., 2003). Most of the yeast kinetochore proteins are found in biochemically distinct complexes known as the CBF3, CTF19/COMA, MTW1, NDC80, and DAM1 complexes that seem to assemble on a single centromeric nucleosome (Meluh et al., 1998). Although the exact architecture of the kinetochore is not known, dependency relationships subdivide the kinetochore into inner, central, and outer domains. The inner kinetochore contains the CBF3 complex (Ndc10, Cep3, Skp1, and Ctf13) as well as the DNA binding proteins Mif2, Cbf1, and the yeast centromeric histone H3 variant (CenH3) Cse4. CBF3 binds directly to the centromeric DNA and is thought to nucleate kinetochore assembly because all kinetochore proteins require it for localization (Russell et al., 1999;Goshima and Yanagida, 2000;He et al., 2001;Janke et al., 2001Janke et al., , 2002. The central kinetochore contains the MTW1 (Mtw1, Dsn1, Nnf1, and Nsl1) and CTF19/COMA (Ctf19, Mcm16, Mcm19, Mcm21, Mcm22, Ctf3, Chl4, Okp1, Ame1, Iml3, Nkp1, and Nkp2) complexes. CTF19/COMA can be further divided into two subcomplexes, with Ame1...

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

De Novo Kinetochore Assembly Requires the Centromeric Histone H3 Variant

Collins

Castillo

Tatsutani

et al. 2005

MBoC

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“…Remarkable progress has been made in the understanding of centromeres since the identification of the first centromere proteins in the mid1980s (Earnshaw and Rothfield 1985;Palmer et al 1987). Given that the rate at which new centromere proteins are being identified appears to be slowing, we may be nearing a complete parts list of centromere proteins.…”

Section: Discussionmentioning

confidence: 99%

“…2). CENP-A was initially discovered as a human autoantigen in CREST syndrome patients, and was subsequently shown to copurify with histones, be present in purified nucleosomes, and be essential across eukaryotic model organisms, as mutation or disruption of CENP-A causes a complete failure in centromere and kinetochore formation (Earnshaw and Rothfield 1985;Earnshaw et al 1986;Palmer et al 1987Palmer et al , 1991Sullivan et al 1994). In humans, functional centromeres always contain CENP-A, including "neocentromeres" that form on noncentromeric chromosomal loci (Saffery et al 2000;Lo et al 2001;Warburton, 2004).…”

Section: Cenp-a: the Centromere-specific Histonementioning

confidence: 99%

The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis

Westhorpe

Straight

2014

Cold Spring Harb Perspect Biol

142

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A fundamental challenge for the survival of all organisms is maintaining the integrity of the genome in all cells. Cells must therefore segregate their replicated genome equally during each cell division. Eukaryotic organisms package their genome into a number of physically distinct chromosomes, which replicate during S phase and condense during prophase of mitosis to form paired sister chromatids. During mitosis, cells form a physical connection between each sister chromatid and microtubules of the mitotic spindle, which segregate one copy of each chromatid to each new daughter cell. The centromere is the DNA locus on each chromosome that creates the site of this connection. In this review, we present a brief history of centromere research and discuss our current knowledge of centromere establishment, maintenance, composition, structure, and function in mitosis.

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“…The core domain of CENH3 was called CENP-A targeting domain (CATD), which confers kinetochore formation and centromere targeting. CENH3 (CENP-A) was first identified in humans through biochemical studies [24]. Partial sequence analysis indicated that it was a new histone and essential for centromeres [25].…”

Section: Centromeric Histone H3 Variant Cenh3mentioning

confidence: 99%

Recent advances in plant centromere biology

Feng

Liu

et al. 2015

Sci. China Life Sci.

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The centromere, which is one of the essential parts of a chromosome, controls kinetochore formation and chromosome segregation during mitosis and meiosis. While centromere function is conserved in eukaryotes, the centromeric DNA sequences evolve rapidly and have few similarities among species. The histone H3 variant CENH3 (CENP-A in human), which mostly exists in centromeric nucleosomes, is a universal active centromere mark in eukaryotes and plays an essential role in centromere identity determination. The relationship between centromeric DNA sequences and centromere identity determination is one of the intriguing questions in studying centromere formation. Due to the discoveries in the past decades, including "neocentromeres" and "centromere inactivation", it is now believed that the centromere identity is determined by epigenetic mechanisms. This review will present recent progress in plant centromere biology. centromere, epigenetics, CENH3

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A 17-kD centromere protein (CENP-A) copurifies with nucleosome core particles and with histones

Cited by 385 publications

References 49 publications

De Novo Kinetochore Assembly Requires the Centromeric Histone H3 Variant

De Novo Kinetochore Assembly Requires the Centromeric Histone H3 Variant

The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis

Recent advances in plant centromere biology

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