A mutation in CSE4, an essential gene encoding a novel chromatin-associated protein in yeast, causes chromosome nondisjunction and cell cycle arrest at mitosis.

Stoler, Sam; Keith, Kevin C.; Curnick, Kathie E.; Fitzgerald-Hayes, Molly

doi:10.1101/gad.9.5.573

Cited by 376 publications

(316 citation statements)

References 60 publications

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“…The Nterminal half of Cse4p is unique. Therefore Cse4p could be part of a specialized nucleosome that participates in the formation of the kinetochore [21,22]. However, it has yet to be addressed whether Cse4p physically interacts with the CEN DNA or with the CEN DNA binding proteins and whether the centromere chromatin is altered in cse4 mutants.…”

Section: Other Putative Structural Kinetochore Proteinsmentioning

confidence: 99%

The Saccharomyces cerevisiae kinetochore

Lechner¹,

Ortiz²

1996

FEBS Letters

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Accurate chromosome segregation is dependent on a specialized chromosomal structure, the kinetochore/centromere. The only essential constituent of the S. cerevisiae kinetochore established today is CBF3, a multisubunit complex that binds to S. cerevisiae centromere DNA. Therefore CBF3 and its four components, Cbf3a, Cbf3b, Cbf3c and Cbf3d, will form the centerpiece of this review. In addition, we will describe proteins that are putatively involved in kinetochore function specifically in the context with CBF3 interaction. Furthermore, we discuss the role of the S. cerevisiae kinetochores in a putative cell cycle checkpoint control and in microtubule attachment. Key words:Centromere; Kinetochore; CBF3; Saccharomyces cerevisiae Recent reviews that describe the S. cerevisiae kinetochore are available [1,5,6]. This review focuses on the protein components of the S. cerevisiae kinetochore. First we describe proteins that physically interact with the CEN DNA and we emphasize the analysis of CBF3 (_centromere DNA binding factor), a key component of the S. cerevisiae kinetochore. Second we describe proteins that are putatively involved in kinetochore function (as structural components or regulators) as deduced from genetic interactions with CEN DNA or CEN DNA binding proteins. Finally we discuss the role of the S. cerevisiae kinetochore as a putative cell cycle checkpoint and in microtubule interaction. CEN DNA binding proteins

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Section: Other Putative Structural Kinetochore Proteinsmentioning

confidence: 99%

The Saccharomyces cerevisiae kinetochore

Lechner¹,

Ortiz²

1996

FEBS Letters

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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).…”

mentioning

confidence: 99%

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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“…All strains were grown in rich medium (YPD) at room temperature, unless indicated otherwise. The nnf1-17 strain (Euskirchen 2002) was a kind gift from Ghia Euskirchen, ipl1-321 (Chan and Botstein 1993) and cse4-1 (Stoler et al 1995) were a kindly provided by Peter Sorger. Strain for the chromosome loss assay was a kind gift from Andrew Murray.…”

Section: Media Yeast Strains and Plasmidsmentioning

confidence: 99%

“…In order to get further insights into the putative involvement of Ber1 in kinetochore function, the ber1 mutant was crossed with temperature-sensitive mutants of the following essential components of the kinetochore: the aurora kinase Ipl1 (Chan and Botstein 1993), which regulates microtubule-kinetochore attachment (Buvelot et al 2003); Nnf1, a component of the central MIND kinetochore complex that contributes to linking the inner and outer kinetochore layers (De Wulf et al 2003); Ndc10 (Goh and Kilmartin 1993), which is a key component of the inner kinetochore that is necessary for kinetochore assembly (Espelin et al 2003); and Cse4 (Stoler et al 1995), a centromere-speciWc histone variant involved in kinetochore assembly (Meluh et al 1998). Altogether, these proteins are quite representative of the diVerent components of the kinetochore.…”

Section: Conwrmation Of the Involvement Of Ber1 In Kinetochore Functionmentioning

confidence: 99%

The evolutionary conserved BER1 gene is involved in microtubule stability in yeast

et al. 2007

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In yeast, microtubules are dynamic Wlaments necessary for spindle and nucleus positioning, as well as for proper chromosome segregation. We identify a function for the yeast gene BER1 (Benomyl REsistant 1) in microtubule stability. BER1 belongs to an evolutionary conserved gene family whose founding member Sensitivity to Red light Reduced is involved in red-light perception and circadian rhythms in Arabidopsis. Here, we present data showing that the ber1 mutant is aVected in microtubule stability, particularly in presence of microtubuledepolymerising drugs. The pattern of synthetic lethal interactions obtained with the ber1 mutant suggests that Ber1 may function in N-terminal protein acetylation. Our work thus suggests that microtubule stability might be regulated through this post-translational modiWcation on yetto-be determined proteins.

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A mutation in CSE4, an essential gene encoding a novel chromatin-associated protein in yeast, causes chromosome nondisjunction and cell cycle arrest at mitosis.

Cited by 376 publications

References 60 publications

The Saccharomyces cerevisiae kinetochore

The Saccharomyces cerevisiae kinetochore

De Novo Kinetochore Assembly Requires the Centromeric Histone H3 Variant

The evolutionary conserved BER1 gene is involved in microtubule stability in yeast

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