Implication of a novel multiprotein Dam1p complex in outer kinetochore function

Cheeseman, Iain M.; Brew, Christine Taylor; Wolyniak, Michael J.; Desai, Arshad; Anderson, Scott; Muster, Nemone; Yates, John R.; Huffaker, Tim C.; Drubin, David G.; Barnes, Georjana

doi:10.1083/jcb.200109063

Cited by 165 publications

(157 citation statements)

References 43 publications

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“…First, Ask1 was phosphorylated in a cell cycle dependent manner giving rise to an altered electrophoretic mobility. During the course of these studies, this was also observed by Cheeseman et al 23 We observed that the timing of phosphorylation correlated well with the timing of Cdc28 activity in vivo. Furthermore, arresting cells in G 1 , S or M with drugs gave phosphorylation patterns consistent with the known levels of Cdc28 activity during those periods of the cycle.…”

Section: Discussionsupporting

confidence: 87%

“…It is composed of at least 9 protein components, including Ask1, Dam1, Duo1, Dad1, Dad2, Dad3, Spc19, Spc34 and Hsk2 (Helper of Ask1) (YDR320C-A, Li and Elledge, in preparation), all of which are essential. [23][24][25] The kinetochore is not a static structure, but a dynamic one that must undergo substantial regulation to insure that proper microtubule attachment and segregation of chromosomes occur. Two key aspects of kinetochore function are the capture of microtubules and the bipolar attachment to microtubules.…”

Section: Introductionmentioning

confidence: 99%

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The DASH Complex Component Ask1 Is a Cell Cycle-Regulated Cdk Substrate inSaccharomyces cerevisiae

Elledge²

2003

Cell Cycle

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© 2 0 0 3 L a n d e s B i o s c i e n c e . N o t f o r d i s t r i b u t i o n . ABSTRACTThe proper timing and fidelity of cell cycle transitions is critical for the survival of organisms. Cyclin-dependent kinases orchestrate many cell cycle transitions in eukaryotes including S phase entry and mitosis. Accurate chromosome segregation during mitosis is one of the key events regulated by the cell cycle and many proteins function together to ensure the fidelity of this process. In S. cerevisiae, the DASH complex is essential for chromosome segregation. The DASH complex binds to microtubules and kinetochores and regulates their association. Here we report that Ask1, one component of DASH, is phosphorylated during the cell cycle. This phosphorylation is dependent on Cdks in vivo, and in vitro Cdc28 can phosphorylate Ask1. We identify two Cdk phosphorylation sites in Ask1 and find that the phosphorylation of Ask1 is important for its full activity in vivo. Thus, the DASH complex is directly regulated by cyclin-dependent kinases to facilitate chromosome segregation.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

The DASH Complex Component Ask1 Is a Cell Cycle-Regulated Cdk Substrate inSaccharomyces cerevisiae

Elledge²

2003

Cell Cycle

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“…The S. cerevisiae kinetochore complex is composed of four subcomplexes: MIND, NDC80, COMA, and Ctf19 (De Wulf et al, 2003). In addition, the DASH complex is localized at the kinetochore and the spindle and is required for spindle attachment to the kinetochore (Cheeseman et al, 2001;Li et al, 2002). The S. cerevisiae DASH complex is composed of 10 proteins that localize at the kinetochore and the spindle (Miranda et al, 2005;Westermann et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Reconstruction of the Kinetochore during Meiosis in Fission Yeast Schizosaccharomyces pombe

Hayashi

Asakawa

Haraguchi

et al. 2006

MBoC

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During the transition from mitosis to meiosis, the kinetochore undergoes significant reorganization, switching from a bipolar to a monopolar orientation. To examine the centromere proteins that are involved in fundamental reorganization in meiosis, we observed the localization of 22 mitotic and 2 meiotic protein components of the kinetochore during meiosis in living cells of the fission yeast. We found that the 22 mitotic proteins can be classified into three groups: the Mis6-like group, the NMS (Ndc80-Mis12-Spc7) group, and the DASH group, based on their meiotic behavior. Mis6-like group proteins remain at the centromere throughout meiosis. NMS group proteins disappear from the centromere at the onset of meiosis and reappear at the centromere in two steps in late prophase. DASH group proteins appear shortly before metaphase of meiosis I. These observations suggest that Mis6-like group proteins constitute the structural basis of the centromere and that the NMS and DASH group proteins reassemble to establish the functional metaphase kinetochore. On the other hand, the meiosis-specific protein Moa1, which plays an important role in forming the meiotic monopolar kinetochore, is loaded onto the centromere significantly earlier than the NMS group, whereas another meiosis-specific protein, Sgo1, is loaded at times similar to the NMS group.

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“…In this organism, mitotic spindles have been shown to be highly compromised in various mutants of the Dam1 complex (8,9,16,24). All 10 proteins of the Dam1 complex are essential for viability, localized at the KT throughout the cell cycle, and help in chromosome segregation by forming rings around the MTs in S. cerevisiae (48).…”

mentioning

confidence: 99%

The Essentiality of the Fungus-Specific Dam1 Complex Is Correlated with a One-Kinetochore-One-Microtubule Interaction Present throughout the Cell Cycle, Independent of the Nature of a Centromere

Thakur

Sanyal

2011

Eukaryot Cell

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A fungus-specific outer kinetochore complex, the Dam1 complex, is essential in Saccharomyces cerevisiae, nonessential in fission yeast, and absent from metazoans. The reason for the reductive evolution of the functionality of this complex remains unknown. Both Candida albicans and Schizosaccharomyces pombe have regional centromeres as opposed to the short-point centromeres of S. cerevisiae. The interaction of one microtubule per kinetochore is established both in S. cerevisiae and C. albicans early during the cell cycle, which is in contrast to the multiple microtubules that bind to a kinetochore only during mitosis in S. pombe. Moreover, the Dam1 complex is associated with the kinetochore throughout the cell cycle in S. cerevisiae and C. albicans but only during mitosis in S. pombe. Here, we show that the Dam1 complex is essential for viability and indispensable for proper mitotic chromosome segregation in C. albicans. The kinetochore localization of the Dam1 complex is independent of the kinetochoremicrotubule interaction, but the function of this complex is monitored by a spindle assembly checkpoint. Strikingly, the Dam1 complex is required to prevent precocious spindle elongation in premitotic phases. Thus, constitutive kinetochore localization associated with a one-microtubule-one kinetochore type of interaction, but not the length of a centromere, is correlated with the essentiality of the Dam1 complex.The separation of sister chromatids during mitosis is driven by a dynamic interaction between two macromolecular structures: (i) the kinetochore (KT), a complex proteinaceous structure built on the centromere DNA (10, 47), and (ii) the mitotic spindle formed by microtubules (MTs). The process of chromosome segregation has been studied extensively in a wide range of organisms, from simple unicellular yeasts to humans. While the major sequence of events required for chromosome segregation remains the same, a few species-specific differences exist. The microtubule organizing centers (MTOCs) in budding yeasts, called spindle pole bodies (SPBs), are embedded in the nuclear envelope and assemble an intranuclear mitotic spindle (5). Thus, the interaction of spindle MTs with KTs does not require the breakdown of the nuclear envelope during closed mitosis in budding yeasts, and the KT-MT interaction is established early in the cell cycle (12, 23). The fission yeast Saccharomyces pombe also undergoes closed mitosis (23), but SPBs remain outside the nuclear envelope during interphase (27) and spindle MTs are nucleated and interact with KTs only when the duplicated SPBs enter the nuclear membrane following mitotic initiation (14). Metazoan cells, in contrast, undergo open mitosis (22,45) in which the MTs, originating from MTOCs, gain access to KTs only when the nuclear envelope breaks down during mitosis. Finally, the number of MTs that bind to a single chromosome differs in these organisms: in Saccharomyces cerevisiae only one MT binds per KT (52), in S. pombe two or three MTs bind per KT (13), and in metazoans multipl...

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Implication of a novel multiprotein Dam1p complex in outer kinetochore function

Cited by 165 publications

References 43 publications

The DASH Complex Component Ask1 Is a Cell Cycle-Regulated Cdk Substrate inSaccharomyces cerevisiae

The DASH Complex Component Ask1 Is a Cell Cycle-Regulated Cdk Substrate inSaccharomyces cerevisiae

Reconstruction of the Kinetochore during Meiosis in Fission Yeast Schizosaccharomyces pombe

The Essentiality of the Fungus-Specific Dam1 Complex Is Correlated with a One-Kinetochore-One-Microtubule Interaction Present throughout the Cell Cycle, Independent of the Nature of a Centromere

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