Crystal Structure of the Human Centromere Protein B (CENP-B) Dimerization Domain at 1.65-Å Resolution

Tawaramoto, Maki S.; Park, Sam Yong; Tanaka, Yoshinori; Nureki, Osamu; Kurumizaka, Hitoshi; Yokoyama, Shigeyuki

doi:10.1074/jbc.m310388200

Cited by 28 publications

(24 citation statements)

References 40 publications

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“…Mammalian CENP-Bs form homodimers through their conserved carboxy-terminal domain 27,28 . We explored whether Abp1 could form dimers that might contribute to 'bundling' Tf2 elements into Tf bodies.…”

Section: Dispersed Tf2 Elements Cluster Into Tf Bodiesmentioning

confidence: 99%

Host genome surveillance for retrotransposons by transposon-derived proteins

Cam¹,

Noma²,

Ebina

et al. 2007

Nature

161

241

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Transposable elements and their remnants constitute a substantial fraction of eukaryotic genomes. Host genomes have evolved defence mechanisms, including chromatin modifications and RNA interference, to regulate transposable elements. Here we describe a genome surveillance mechanism for retrotransposons by transposase-derived centromeric protein CENP-B homologues of the fission yeast Schizosaccharomyces pombe. CENP-B homologues of S. pombe localize at and recruit histone deacetylases to silence Tf2 retrotransposons. CENP-Bs also repress solo long terminal repeats (LTRs) and LTR-associated genes. Tf2 elements are clustered into 'Tf' bodies, the organization of which depends on CENP-Bs that display discrete nuclear structures. Furthermore, CENP-Bs prevent an 'extinct' Tf1 retrotransposon from re-entering the host genome by blocking its recombination with extant Tf2, and silence and immobilize a Tf1 integrant that becomes sequestered into Tf bodies. Our results reveal a probable ancient retrotransposon surveillance pathway important for host genome integrity, and highlight potential conflicts between DNA transposons and retrotransposons, major transposable elements believed to have greatly moulded the evolution of genomes.

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Section: Dispersed Tf2 Elements Cluster Into Tf Bodiesmentioning

confidence: 99%

Host genome surveillance for retrotransposons by transposon-derived proteins

Cam¹,

Noma²,

Ebina

et al. 2007

Nature

161

241

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“…It has two, small helix-turn-helix domains, positioned over the major groove about one DNA turn apart. The C-terminal CENP-B dimerization region consists of a pair of antiparallel α-helices (Tawaramoto et al, 2003). Association with the dimer partner is such that the two N-termini are at opposite ends of the dimer module, and the two DNA-binding domains may therefore associate with distant sites, separated by a large loop.…”

Section: Centromeric Evolutionmentioning

confidence: 99%

Crystal Structure of the Yeast Inner Kinetochore Subunit Cep3p

Bellizzi

Sorger

2007

Structure

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In budding yeast, the four-protein CBF3 complex (Skp1p-Ctf13p-Cep3p-Ndc10p) initiates kinetochore assembly by binding to the CDEIII locus of centromeric DNA. A Cep3p dimer recruits a Skp1p-Ctf13p heterodimer and contacts two sites on CDEIII. We report here the crystal structure, determined at 2.8 A resolution by multiple isomorphous replacement with anomalous scattering, of a truncated Cep3p (Cep3p [47-608]), comprising all but an N-terminal, Zn(2)Cys(6)-cluster, DNA-binding module. Cep3p has a well-ordered structure throughout essentially all of its polypeptide chain, unlike most yeast transcription factors, including those with Zn(2)Cys(6) clusters, such as Gal4p. This difference may reflect an underlying functional distinction: whereas any particular transcription factor must adapt to a variety of upstream activating sites, Cep3p scaffolds kinetochore assembly on centromeres uniformly configured on all 16 yeast chromosomes. We have, using the structure of Cep3p (47-608) and the known structures of Zn(2)Cys(6)-cluster domains, modeled the interaction of Cep3p with CDEIII.

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“…The crystal structure of the C-terminal CENP-B dimerisation domain (amino acids 540-599) consists of two a helices, which are folded into an antiparallel configuration, and forms a dimer with a symmetrical, antiparallel, four-helix bundle structure. [43] Nucleosome reconstitution experiments with canonical his-A C H T U N G T R E N N U N G tones and CENP-B suggest that CENP-B has the potential to modulate nucleosome formation in the vicinity of the CENP-B box. [36] In vitro, CENP-B is able to bind to nucleosomal DNA when the CENP-B box is wrapped within the nucleosome core particle and can induce translational positioning of the nucleosome.…”

Section: Introductionmentioning

confidence: 99%

Assembly of the Inner Kinetochore Proteins CENP‐A and CENP‐B in Living Human Cells

Orthaus¹,

Biskup

Hoffmann

et al. 2007

ChemBioChem

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DNA segregation in mammalian cells during mitosis is an essential cellular process that is mediated by a specific subchromosomal protein complex, the kinetochore. Malfunction of this complex results in aneuploidy and can cause cancer. A subkinetochore complex, the "inner kinetochore", is present at the centromere during the entire cell cycle. Its location seems to be defined by the settlement of CENP-A (CENH3), which replaces histone H3 in centromeric nucleosomes. This suggests that CENP-A can recruit further inner kinetochore proteins by direct binding. Surprisingly, intense in vitro studies could not identify an interaction of CENP-A with any other inner kinetochore protein. Instead, centromere identity seems to be maintained by a unique nucleosome, which might have a modified structure or epigenetic state that serves to distinguish the centromere from the rest of the chromosome. We investigated the association of CENP-A and CENP-B by fluorescence intensity and lifetime-based FRET measurements in living human HEp-2 cells. We observed Förster resonance energy transfer (FRET) between CENP-A and CENP-B at centromere locations; this indicates that these proteins are in the molecular vicinity (<10 nm) of each other. In addition, we analysed protein-protein interactions within the centromeric nucleosome. We could detect energy transfer between CENP-A and histone H4 as well as between CENP-A molecules themselves. On the other hand, no FRET was detected between CENP-A and H2A.1 or H3.1. Our data support the view that two CENP-A molecules are packed with H4, but not with H3, in a single centromeric nucleosome.

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Crystal Structure of the Human Centromere Protein B (CENP-B) Dimerization Domain at 1.65-Å Resolution

Cited by 28 publications

References 40 publications

Host genome surveillance for retrotransposons by transposon-derived proteins

Host genome surveillance for retrotransposons by transposon-derived proteins

Crystal Structure of the Yeast Inner Kinetochore Subunit Cep3p

Assembly of the Inner Kinetochore Proteins CENP‐A and CENP‐B in Living Human Cells

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