Structure of Yeast Kinetochore Ndc10 DNA-binding Domain Reveals Unexpected Evolutionary Relationship to Tyrosine Recombinases

Perriches, Thibaud; Singleton, Martin R.

doi:10.1074/jbc.c111.318501

Cited by 13 publications

(17 citation statements)

References 44 publications

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“…Previous studies have suggested that Ndc10 and Cep3 constitute the DNA-binding activities of the complex. Both Ndc10 and Cep3 are capable of directly binding DNA (Espelin et al, 1997;Purvis & Singleton, 2008;Cho & Harrison, 2011;Perriches & Singleton, 2012); in the case of Cep3, sequence specificity for the CDEIII element is provided by zinc-containing Gal4-type DNA-binding domains (Strunnikov et al, 1995;Espelin et al, 1997). The function of Ctf13 and Skp1 has remained obscure.…”

Section: Introductionmentioning

confidence: 99%

“…Exactly how these pathways contribute to the assembly of mature, centromere-binding proficient CBF3 is still not entirely clear. Crystal structures have been determined of the truncated Cep3 and Ndc10 proteins (Bellizzi et al, 2007;Purvis & Singleton, 2008;Cho & Harrison, 2011;Perriches & Singleton, 2012) as well as full-length Skp1 (Schulman et al, 2000;Orlicky et al, 2003). However, we are missing structural data for Ctf13 and crucially, the intact CBF3 complex.…”

Section: Introductionmentioning

confidence: 99%

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Structural basis for assembly of the CBF3 kinetochore complex

2017

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Eukaryotic chromosomes contain a specialised region known as the centromere, which forms the platform for kinetochore assembly and microtubule attachment. The centromere is distinguished by the presence of nucleosomes containing the histone H3 variant, CENP‐A. In budding yeast, centromere establishment begins with the recognition of a specific DNA sequence by the CBF3 complex. This in turn facilitates CENP‐ACse4 nucleosome deposition and kinetochore assembly. Here, we describe a 3.6 Å single‐particle cryo‐EM reconstruction of the core CBF3 complex, incorporating the sequence‐specific DNA‐binding protein Cep3 together with regulatory subunits Ctf13 and Skp1. This provides the first structural data on Ctf13, defining it as an F‐box protein of the leucine‐rich‐repeat family, and demonstrates how a novel F‐box‐mediated interaction between Ctf13 and Skp1 is responsible for initial assembly of the CBF3 complex.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structural basis for assembly of the CBF3 kinetochore complex

2017

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“…The complex contains four essential proteins that are most commonly referred to as Ndc10 (Cbf3a/ Cbf2/Ctf14/p110) (Doheny et al 1993;Goh and Kilmartin 1993;Jiang et al 1993), Cep3 (Cbf3b/p64) (Lechner 1994;Strunnikov et al 1995), Ctf13 (Cbf3c/p58) (Doheny et al 1993), and Skp1 (Cbf3/p19) (Connelly and Hieter 1996;Stemmann and Lechner 1996). Cep3 has a Zinc-cluster motif found in transcription factors (Dhawale and Lane 1993;Strunnikov et al 1995;Schjerling and Holmberg 1996) and Ndc10 was recently shown to have structural similarity to tyrosine DNA recombinases (Cho and Harrison 2012;Perriches and Singleton 2012), although it does not exhibit catalytic activity or DNA base sequence specificity. Consistent with this, Ndc10 (in the absence of CBF3) can also bind to the CDEII element in vitro as well as other genomic regions that are AT rich, although these activities are not known to be relevant to CBF3 assembly in vivo (Espelin et al 2003).…”

Section: Inner Centromere Binding Proteinsmentioning

confidence: 99%

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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“…Ndc10 is distantly related to the tyrosine DNA recombinases, such as CRE (Cho and Harrison 2012; Perriches and Singleton 2012). Ndc10 may be central to the controversy surrounding the Cse4 nucleosome, as well as the structure of the inner centromere.…”

Section: Characteristics Of Centromere Chromatin—primary Folding Of Amentioning

confidence: 99%

Centromere Structure and Function

Bloom

Costanzo

2017

Progress in Molecular and Subcellular Biology

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The centromere is the genetic locus that specifies the site of kinetochore assembly, where the chromosome will attach to the kinetochore microtubule. The pericentromere is the physical region responsible for the geometry of bi-oriented sister kinetochores in metaphase. In budding yeast the 125 bp point centromere is sufficient to specify kinetochore assembly. The flanking region is enriched (3X) in cohesin and condensin relative to the remaining chromosome arms. The enrichment spans about 30-50 kb around each centromere. We refer to the flanking chromatin as the pericentromere in yeast. In mammals, a 5-10 Mb region dictates where the kinetochore is built. The kinetochore interacts with a very small fraction of DNA on the surface of the centromeric region. The remainder of the centromere lies between the sister kinetochores. This is typically called centromere chromatin. The chromatin sites that directly interface to microtubules cannot be identified due to the repeated sequence within the mammalian centromere. However in both yeast and mammals, the total amount of DNA between the sites of microtubule attachment in metaphase is highly conserved. In yeast the 16 chromosomes are clustered into a 250 nm diameter region, and 800 kb (16 × 50 kb) or ~1 Mb of DNA lies between sister kinetochores. In mammals, 5-10 Mb lies between sister kinetochores. In both organisms the sister kinetochores are separated by about 1 μm. Thus, centromeres of different organisms differ in how they specify kinetochore assembly, but there may be important centromere chromatin functions that are conserved throughout phylogeny. Recently, centromeric chromatin has been reconstituted in vitro using alpha satellite DNA revealing unexpected features of centromeric DNA organization, replication, and response to stress. We will focus on the conserved features of centromere in this review.

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Structure of Yeast Kinetochore Ndc10 DNA-binding Domain Reveals Unexpected Evolutionary Relationship to Tyrosine Recombinases

Cited by 13 publications

References 44 publications

Structural basis for assembly of the CBF3 kinetochore complex

Structural basis for assembly of the CBF3 kinetochore complex

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

Centromere Structure and Function

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