Chl4p and Iml3p Are Two New Members of the Budding Yeast Outer Kinetochore

Pot, Isabelle; Measday, Vivien; Snydsman, Brian E.; Cagney, Gerard; Fields, Stanley; Davis, Trisha N.; Muller, Eric G D; Hieter, Philip

doi:10.1091/mbc.e02-08-0517

Cited by 62 publications

(85 citation statements)

References 48 publications

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“…Ctf13 has an F-box that binds to Skp1, consistent with its role as both an SCF scaffold and a substrate (Zhou and Howley 1998;Galan and Peter 1999). This likely (Meluh and Koshland 1995) CENP-C Cse4 (Meluh et al 1998) CENP-A Ctf19 (Ortiz et al 1999) CENP-P Okp1 (Ortiz et al 1999) CENP-Q Mcm21 (Ortiz et al 1999) CENP-O Ame1 (De Wulf et al 2003) CENP-U Chl4 (Mythreye and Bloom 2003;Pot et al 2003) CENP-N Cnn1 (De Wulf et al 2003) CENP-T Wip1 (Schleiffer et al 2012) CENP-W Mhf1 (Schleiffer et al 2012) CEN-S Mhf2 (Schleiffer et al 2012) CENP-X Mcm16 (Measday et al 2002) CENP-H Ctf3 (Measday et al 2002) CENP-I Mcm22 (Measday et al 2002) CENP-K Iml3/Mcm19 (Pot et al 2003) CENP-L Nkp1 (Cheeseman et al 2002) Nkp2 (Cheeseman et al 2002) Ybp2 (Ohkuni et al 2008 Kip1 (Tytell and Sorger 2006) BimC family Kip3 (Tytell and Sorger 2006) Kinesin-8 Cin8 Kinesin-5 Kar3 (Tanaka et al 2005) Kinesin-14 MAPS Slk19 (Zeng et al 1999) Bik1 CLIP-170 Stu1 ) CLASP Stu2 XMAP215…”

Section: Inner Centromere Binding Proteinsmentioning

confidence: 83%

“…COMA and interacting proteins Additional components of the yeast inner kinetochore include the COMA subcomplex (Ctf19, Okp1, Mcm21 and Ame1), as well as many additional interacting proteins (see Table 1) (Kroll et al 1996;Sanyal et al 1998;Hyland et al 1999;Ortiz et al 1999;Poddar et al 1999;Cheeseman et al 2002;Measday et al 2002;De Wulf et al 2003;Pot et al 2003;Ohkuni et al 2008;Schleiffer et al 2012). With the exception of Okp1 and Ame1, most of these proteins are nonessential and may have redundant functions.…”

Section: Inner Centromere Binding Proteinsmentioning

confidence: 99%

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The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

2013

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The propagation of all organisms depends on the accurate and orderly segregation of chromosomes in mitosis and meiosis. Budding yeast has long served as an outstanding model organism to identify the components and underlying mechanisms that regulate chromosome segregation. This review focuses on the kinetochore, the macromolecular protein complex that assembles on centromeric chromatin and maintains persistent load-bearing attachments to the dynamic tips of spindle microtubules. The kinetochore also serves as a regulatory hub for the spindle checkpoint, ensuring that cell cycle progression is coupled to the achievement of proper microtubule-kinetochore attachments. Progress in understanding the composition and overall architecture of the kinetochore, as well as its properties in making and regulating microtubule attachments and the spindle checkpoint, is discussed. TABLE OF CONTENTS Abstract 817Introduction 818

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Section: Inner Centromere Binding Proteinsmentioning

confidence: 83%

Section: Inner Centromere Binding Proteinsmentioning

confidence: 99%

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

2013

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“…CTF19, CTF3, MCM16, MCM22, CHL4, and IML3 encode proteins that function at the outer kinetochore Pot et al 2003). The outer kinetochore is thought to provide a link between the centromere-binding inner kinetochore proteins and microtubule-binding proteins.…”

Section: à11mentioning

confidence: 99%

Telomerase Is Essential to Alleviate Pif1-Induced Replication Stress at Telomeres

et al. 2009

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Pif1, an evolutionarily conserved helicase, negatively regulates telomere length by removing telomerase from chromosome ends. Pif1 has also been implicated in DNA replication processes such as Okazaki fragment maturation and replication fork pausing. We find that overexpression of Saccharomyces cervisiae PIF1 results in dose-dependent growth inhibition. Strong overexpression causes relocalization of the DNA damage response factors Rfa1 and Mre11 into nuclear foci and activation of the Rad53 DNA damage checkpoint kinase, indicating that the toxicity is caused by accumulation of DNA damage. We screened the complete set of $4800 haploid gene deletion mutants and found that moderate overexpression of PIF1, which is only mildly toxic on its own, causes growth defects in strains with mutations in genes involved in DNA replication and the DNA damage response. Interestingly, we find that telomerase-deficient strains are also sensitive to PIF1 overexpression. Our data are consistent with a model whereby increased levels of Pif1 interfere with DNA replication, causing collapsed replication forks. At chromosome ends, collapsed forks result in truncated telomeres that must be rapidly elongated by telomerase to maintain viability.

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“…ChIP experiments and primers used for polymerase chain reaction (PCR) analysis were performed as described previously (Measday et al, 2002;Pot et al, 2003). The linear range for PCR analysis was determined, and dilutions used for Figure …”

Section: Chromatin Immunoprecipitation (Chip) Assaysmentioning

confidence: 99%

Spc24 and Stu2 Promote Spindle Integrity When DNA Replication Is Stalled

McQueen

Cuschieri²,

Vogel

et al. 2007

MBoC

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The kinetochore, a protein complex that links chromosomes to microtubules (MTs), is required to prevent spindle expansion during S phase in budding yeast, but the mechanism of how the kinetochore maintains integrity of the bipolar spindle before mitosis is not well understood. Here, we demonstrate that a mutation of Spc24, a component of the conserved Ndc80 kinetochore complex, causes lethality when cells are exposed to the DNA replication inhibitor hydroxyurea (HU) due to premature spindle expansion and segregation of incompletely replicated DNA. Overexpression of Stu1, a CLASP-related MT-associated protein or a truncated form of the XMAP215 orthologue Stu2 rescues spc24-9 HU lethality and prevents spindle expansion. Truncated Stu2 likely acts in a dominant-negative manner, because overexpression of full-length STU2 does not rescue spc24-9 HU lethality, and spindle expansion in spc24-9 HU-treated cells requires active Stu2. Stu1 and Stu2 localize to the kinetochore early in the cell cycle and Stu2 kinetochore localization depends on Spc24. We propose that mislocalization of Stu2 results in premature spindle expansion in S phase stalled spc24-9 mutants. Identifying factors that restrain spindle expansion upon inhibition of DNA replication is likely applicable to the mechanism by which spindle elongation is regulated during a normal cell cycle. INTRODUCTIONPreserving the integrity of the genome is a fundamental requirement for eukaryotic cell viability. DNA replication must be completed before segregation of the chromosomes to prevent the transmission of partially replicated chromosomes to daughter cells. In the budding yeast Saccharomyces cerevisiae, cells undergo a closed mitosis and the microtubule (MT) organizing centers, or spindle pole bodies (SPBs), are imbedded in the nuclear envelope. SPB duplication begins at the end of anaphase and spindle formation begins during S phase when duplicated SPBs separate from each other (Adams and Kilmartin, 1999;Jaspersen and Winey, 2004). Because chromosomes remain attached to kinetochore MTs throughout the cell cycle, spindle expansion must be restrained until all 16 chromosomes have duplicated and kinetochores on sister chromatids have formed bipolar MT attachments. When DNA replication is stalled by hydroxyurea (HU) treatment, cells arrest with a large bud, an undivided nucleus positioned at the mother-bud neck and a short bipolar spindle (Allen et al., 1994). Maintaining a short spindle is crucial for cell survival during HU-induced arrest, which activates the DNA replication checkpoint effectors Mec1 and Rad53 (Kolodner et al., 2002). When mec1 and rad53 mutants are treated with HU, the DNA replication checkpoint is not activated, and, as a result, replication forks are not stabilized, the spindle expands, and unequal division of incompletely replicated nuclear material occurs-all of these events contribute to cell lethality (Allen et al., 1994;Weinert et al., 1994;Lopes et al., 2001).In human cells, stalled replication forks activate the ataxia telangiectasia mutat...

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Chl4p and Iml3p Are Two New Members of the Budding Yeast Outer Kinetochore

Cited by 62 publications

References 48 publications

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

Telomerase Is Essential to Alleviate Pif1-Induced Replication Stress at Telomeres

Spc24 and Stu2 Promote Spindle Integrity When DNA Replication Is Stalled

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