Centromere function requires the proper coordination of several subfunctions, such as kinetochore assembly, sister chromatid cohesion, binding of kinetochore microtubules, orientation of sister kinetochores to opposite spindle poles, and their movement towards the spindle poles. Centromere structure appears to be organized in different, separable domains in order to accomplish these functions. Despite the conserved nature of centromere functions, the molecular genetic definition of the DNA sequences that form a centromere in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, in the fruit fly Drosophila melanogaster, and in humans has revealed little conservation at the level of centromere DNA sequences. Also at the protein level few centromere proteins are conserved in all of these four organisms and many are unique to the different organisms. The recent analysis of the centromere structure in the yeast S. pombe by electron microscopy and detailed immunofluorescence microscopy of ...
The histone protein CenH3 is both necessary and sufficient to trigger the formation of centromeres and pass them on from 1 generation to the next. Centromeres are specialised regions of the genome, which can be identified under the microscope as the primary constriction in X-shaped chromosomes. The cell skeleton, which distributes the chromosomes to the two daughter cells during cell division, attaches to the centromeres. In most organisms the position of the centromere is not determined by the DNA sequence. Scientists from the Max Planck Institute of Immunobiology and Epigenetics in Freiburg have succeeded in demonstrating that the position, function and inheritance of the centromere are determined by the histone CenH3, a DNA packaging protein. This discovery may help to further the development of artificial human chromosomes, which could be used for gene therapies in medicine.. Centromeres provide a platform for the development of a protein complex known as the kinetochore. During cell ...
Our results show for the first time that mouse SGO2 localizes at the inner centromere domain during both meiotic and mitotic divisions, in the same way as its orthologue Sgo2 in fission yeast (Kitajima et al, 2004; Rabitsch et al, 2004). SGO2 and RAD21 colocalize and show a double cornet arrangement at the inner centromere domain below the closely associated sister kinetochores during metaphase I and anaphase I. By contrast, REC8 colocalizes only with the vertical region of the T‐shaped SGO2 signals during these stages (supplementary Fig 4 online). These results show that there are two different cohesin complexes with either RAD21 or REC8 at the inner domain of metaphase I and anaphase I centromeres, and that these complexes coexist only at the vertical region of the T‐shaped SGO2 signals. Thus, SGO2, as has been proposed for Sgo1 in Drosophila and yeast meiosis (Kitajima et al, 2004; Marston et al, 2004; Rabitsch et al, 2004; Clarke et al, 2005), could protect centromeric cohesin ...
The accurate distribution of genetic information to daughter cells during cell division relies on the physical attachment of chromosomes to spindle microtubules mediated by kinetochores. Kinetochores are large protein assemblies deposited at specific chromosomal loci known as centromeres [1], [2], [3]. Defective centromere function results in chromosome segregation errors that can contribute to genomic instability implicated in cancer [4]. Hence, understanding the molecular mechanisms that promote kinetochore establishment and maintenance at centromeres is of prime importance.. The location of most eukaryotic centromeres is determined by the assembly of specialized chromatin composed of nucleosomes in which canonical histone H3 is replaced by the centromere‐specific H3 variant CENP‐A in vertebrates and Cnp1 (CENP‐ACnp1) in Schizosaccharomyces pombe [3], [5]. Thus, the establishment and maintenance of kinetochores requires CENP‐A to be recruited to and deposited at centromeres. In S. ...
Centromere DNA element II (CDEII) of budding yeast centromeres is an AT-rich sequence essential for centromere (CEN) function. Sequence analysis of Saccharomyces cerevisiae CDEIIs revealed that A(5-7)/T(5-7) tracts are statistically overrepresented at the expense of AA/TT and alternating AT. To test the hypothesis that this nonrandom sequence organization is functionally important, a CEN library in which the CDEII sequences were randomized was generated. The library was screened for functional and nonfunctional members following centromere replacement in vivo. Functional CENs contained CDEIIs with the highly biased A(n)/T(n) run distribution of native centromeres, while nonfunctional CDEIIs resembled those picked from the library at random. Run content, defined as the fraction of residues present in runs of four or more nucleotides, of the functional and nonfunctional CDEII populations differed significantly (P | 0.001). Computer searches of the genome for regions with an A + T content comparable to
We have employed a system that utilizes homologous pairs of human DNA-derived yeast artificial chromosomes (YACs) as marker chromosomes to assess the specific role(s) of conserved centromere DNA elements (CDEI, CDEII and CDEIII) in meiotic chromosome disjunction fidelity. Thirteen different centromere (CEN) mutations were tested for their effects on meiotic centromere function. YACs containing a wild-type CEN DNA sequence segregate with high fidelity in meiosis I (99% normal segregation) and in meiosis II (96% normal segregation). YACs containing a 31-bp deletion mutation in centromere DNA element II (CDEII delta 31) in either a heterocentric (mutant/wild type), homocentric (mutant/mutant) or monosomic (mutant/--) YAC pair configuration exhibited high levels (16-28%) of precocious sister-chromatid segregation (PSS) and increased levels (1-6%) of nondisjunction meiosis I (NDI). YACs containing this mutation also exhibit high levels (21%) of meiosis II nondisjunction. Interestingly, significant ...
The HTR12 protein is a centromere-specific histone H3 variant in A. thaliana, and was shown to colocalize with the 180 bp repetitive sequences of all centromeres (Talbert et al., 2002). The Zea mays centromeric histone H3, CENH3 was also detected at the kinetochore regions of the centromere and colocalized with centromere-specific tandem repeat CentC and with centromeric retroelement CRM (Zhong et al., 2002). These results indicate wide conservation of CENP-A-like proteins and their close relationship to the centromeric satellites. In our study, the spatial relationship between HTR12 protein and 180 bp repetitive sequences was investigated by sequential combination of immunolabeling and FISH. In the cell cultures studied here, drastic changes in the copy numbers of 180 bp repetitive sequences had occurred, however, all chromosomes carried the 180 bp repetitive sequences despite their variation in size (Fig. 1E,F). For chromosomes with low numbers of 180 bp repetitive sequences, ...
TY - JOUR. T1 - Involvement of the spliceosomal U4 small nuclear RNA in heterochromatic gene silencing at fission yeast centromeres. AU - Chinen, Madoka. AU - Morita, Misato. AU - Fukumura, Kazuhiro. AU - Tani, Tokio. PY - 2010/2/19. Y1 - 2010/2/19. N2 - prp13-1 is one of the mutants isolated in a screen for defective pre-mRNA splicing at a nonpermissive temperature in fission yeast Schizosaccharomyces pombe. We cloned the prp13+ gene and found that it encodes U4 small nuclear RNA (snRNA) involved in the assembly of the spliceosome. The prp13-1 mutant produced elongated cells, a phenotype similar to cell division cycle mutants, and displays a high incidence of lagging chromosomes on anaphase spindles. The mutant is hypersensitive to the microtubule-destabilizing drug thiabendazole, supporting that prp13-1 has a defect in chromosomal segregation. We found that the prp13-1 mutation resulted in expression of the ura4 + gene inserted in the pericentromeric heterochromatin region and reduced ...
TY - JOUR. T1 - Meiosis-Specific loading of the Centromere-Specific histone CENH3 in Arabidopsis thaliana. AU - Ravi, Maruthachalam. AU - Shibata, Fukashi. AU - Ramahi, Joseph S.. AU - Nagaki, Kiyotaka. AU - Chen, Changbin. AU - Murata, Minoru. AU - Chan, Simon W L. PY - 2011/6. Y1 - 2011/6. N2 - Centromere behavior is specialized in meiosis I, so that sister chromatids of homologous chromosomes are pulled toward the same side of the spindle (through kinetochore mono-orientation) and chromosome number is reduced. Factors required for mono-orientation have been identified in yeast. However, comparatively little is known about how meiotic centromere behavior is specialized in animals and plants that typically have large tandem repeat centromeres. Kinetochores are nucleated by the centromere-specific histone CENH3. Unlike conventional histone H3s, CENH3 is rapidly evolving, particularly in its N-terminal tail domain. Here we describe chimeric variants of CENH3 with alterations in the N-terminal ...
The kinetochore directs accurate chromosome segregation by controlling chromosome movements through interactions with spindle microtubules, and also by serving as a platform for various regulatory pathways. Kinetochores assemble on centromere chromatin marked by nucleosomes containing the centromere-specific histone H3 variant CENP-A (Allshire and Karpen, 2008; Earnshaw and Rothfield, 1985). The interphase centromere complex (ICEN) associates with the CENP-A nucleosome (Izuta et al., 2006; Obuse et al., 2004), and the constitutive-centromere-associated network (CCAN) forms the inner kinetochore (Basilico et al., 2014; Cheeseman and Desai, 2008; Foltz et al., 2006; Gascoigne et al., 2011; Hori et al., 2008; Okada et al., 2006). The CCAN factors CENP-C (Saitoh et al., 1992) and CENP-T act as a crucial platform for the kinetochore during mitosis (Gascoigne et al., 2011; Hori et al., 2008, 2013; Nishino et al., 2013; Przewloka et al., 2011; Rago et al., 2015). CENP-C binds to CENP-A nucleosomes ...
TY - JOUR. T1 - Precise centromere mapping using a combination of repeat junction markers and chromatin immunoprecipitation-polymerase chain reaction. AU - Luce, Amy C.. AU - Sharma, Anupma. AU - Mollere, Oliver S.B.. AU - Wolfgruber, Thomas K.. AU - Nagaki, Kiyotaka. AU - Jiang, Jiming. AU - Presting, Gernot G.. AU - Dawe, R. Kelly. PY - 2006/11/6. Y1 - 2006/11/6. N2 - Centromeres are difficult to map even in species where genetic resolution is excellent. Here we show that junctions between repeats provide reliable single-copy markers for recombinant inbred mapping within centromeres and pericentromeric heterochromatin. Repeat junction mapping was combined with anti-CENH3-mediated ChIP to provide a definitive map position for maize centromere 8.. AB - Centromeres are difficult to map even in species where genetic resolution is excellent. Here we show that junctions between repeats provide reliable single-copy markers for recombinant inbred mapping within centromeres and pericentromeric ...
Neocentromere activation requires centromere juxtaposition: Here we describe irradiation-mutagenesis experiments designed to identify the mechanism of neocentromere formation in D. melanogaster. Prior to this study, two models existed to explain the generation of neocentromeres in Drosophila and Homo sapiens-derepression of latent centromere-competent euchromatic sequences vs. centromere spreading (Choo 1997a, 1998). We distinguished between these models through a genetic assay for neocentromere activation and recovery. Three substrate chromosomes were irradiated, and an identical 290-kb test segment was liberated and genetically assayed for neocentromere activity. The three test segments were identical in molecular structure and differed only in their chromosomal context. In Dpγ238, the test segment was juxtaposed to an active centromere; in Dp8-23, the test segment was juxtaposed to centric, but centromerically inert DNA; in Tγ1337, the test segment was juxtaposed to euchromatin. ...
Centromeres are unique chromatin domains that direct the site of kinetochore formation during mitosis and mediate the movement of chromosomes during cell division. Centromeres contain a unique nucleosome in which histone H3 is replaced by centromere protein A (CENP-A). Because of their unique position in chromatin, the CENP-A nucleosome was hypothesized to determine the site of centromere and kinetochore assembly. In order to test the long held assumption that CENP-A dictates the location of the centromere; we developed a novel de novo centromere formation assay, which provides a new and powerful constructive approach to studying centromeres. This system is based on a LacO array that is stably integrated into the long arm of chromosome 1, far away from the existing centromere. Targeting the CENP-A chaperone HJURP or the Mis18 complex to the LacO array, by fusing them to the LacI repressor, drove the stable recruitment of CENP-A nucleosomes to the LacO array at the non-centromeric locus. ...
Centromeres mediate the conserved and essential process of chromosome segregation, yet centromeric DNA and the centromeric histone, CENP-A, are rapidly evolving. The rapid evolution of loop 1 (L1) of Drosophila CENP-A is thought to modulate the DNA-binding preferences of CENP-A to suppress centromere drive, the preferential transmission of chromosomes with expanded centromeric satellites during female meiosis. Consistent with this model, CENP-A from D. bipectinata (bip) fails to localize to D. melanogaster (mel) centromeres due to amino acid differences between mel and bip L1. Here, I show that this result is, in fact, due to the inability of the mel CENP-A chaperone, CAL1, to incorporate bip CENP-A into chromatin. Co-expression of bip CENP-A and bip CAL1 in mel cells restores centromeric localization, and similar findings apply to other Drosophila species. Furthermore, two co-evolving regions, CENP-A L1 and the CAL1 N-terminus, are identified as critical for lineage-specific CENP-A incorporation.
Centromeres are the differentiated chromosomal domains that specify the mitotic behavior of chromosomes. To examine the molecular basis for the specification of centromeric chromatin, we have cloned a human cDNA that encodes the 17-kD histone-like centromere antigen, CENP-A. Two domains are evident in the 140 aa CENP-A polypeptide: a unique NH2-terminal domain and a 93-amino acid COOH-terminal domain that shares 62% identity with nucleosomal core protein, histone H3. An epitope tagged derivative of CENP-A was faithfully targeted to centromeres when expressed in a variety of animal cells and this targeting activity was shown to reside in the histone-like COOH-terminal domain of CENP-A. These data clearly indicate that the assembly of centromeres is driven, at least in part, by the incorporation of a novel core histone into centromeric chromatin. ...
Centromeres are the specialized chromosomal sites necessary for poleward movement during mitosis and meiosis in eukaryotes. Commonly, a centromere is evident as a prominent constriction within the heterochromatin of each metaphase chromosome. The attachment to and movement of chromosomes along the spindle is mediated by the proteinaceous kinetochores, which form at the centromeres during cell division.. Despite this highly conserved function, centromeric DNA sequences are not conserved between organisms. For example, human centromeres consist of large blocks (200 kb to several megabases) of tandemly repeated 171-bp α-satellite (Willard, 1998), but the sequences can differ from those of apes on homologous chromosomes (Haaf and Willard, 1997). Similarly, Drosophila melanogaster centromeric regions contain blocks of 5- to 12-bp satellite repeats that do not appear to be shared by homologous centromeres of sibling species (Lohe and Brutlag, 1987).. Plant centromeric regions resemble their mammalian ...
Track indicating the location of the centromere sequences. Centromeres are specialized chromatin structures that are required for cell division. These genomic regions are normally defined by long tracts of tandem repeats, or satellite DNA, that contain a limited number of sequence differences to distinguish the linear order of repeat copies. The size and repetitive nature of these regions mean they are typically not represented in reference assemblies. Unlike all previous versions of the human reference assembly, where the centromere regions have been represented by a multi-megabase gap, GRCh38 incorporates centromere reference models that provide an initial genomic description derived from chromosome-assigned whole genome shotgun (WGS) read libraries of alpha satellite. Each reference model provides an approximation of the true array sequence organization. Although the long-range repeat ordering is not expected to represent the true organization, the submissions are expected to provide a ...
Track indicating the location of the centromere sequences. Centromeres are specialized chromatin structures that are required for cell division. These genomic regions are normally defined by long tracts of tandem repeats, or satellite DNA, that contain a limited number of sequence differences to distinguish the linear order of repeat copies. The size and repetitive nature of these regions mean they are typically not represented in reference assemblies. Unlike all previous versions of the human reference assembly, where the centromere regions have been represented by a multi-megabase gap, GRCh38 incorporates centromere reference models that provide an initial genomic description derived from chromosome-assigned whole genome shotgun (WGS) read libraries of alpha satellite. Each reference model provides an approximation of the true array sequence organization. Although the long-range repeat ordering is not expected to represent the true organization, the submissions are expected to provide a ...
Track indicating the location of the centromere sequences. Centromeres are specialized chromatin structures that are required for cell division. These genomic regions are normally defined by long tracts of tandem repeats, or satellite DNA, that contain a limited number of sequence differences to distinguish the linear order of repeat copies. The size and repetitive nature of these regions mean they are typically not represented in reference assemblies. Unlike all previous versions of the human reference assembly, where the centromere regions have been represented by a multi-megabase gap, GRCh38 incorporates centromere reference models that provide an initial genomic description derived from chromosome-assigned whole genome shotgun (WGS) read libraries of alpha satellite. Each reference model provides an approximation of the true array sequence organization. Although the long-range repeat ordering is not expected to represent the true organization, the submissions are expected to provide a ...
Track indicating the location of the centromere sequences. Centromeres are specialized chromatin structures that are required for cell division. These genomic regions are normally defined by long tracts of tandem repeats, or satellite DNA, that contain a limited number of sequence differences to distinguish the linear order of repeat copies. The size and repetitive nature of these regions mean they are typically not represented in reference assemblies. Unlike all previous versions of the human reference assembly, where the centromere regions have been represented by a multi-megabase gap, GRCh38 incorporates centromere reference models that provide an initial genomic description derived from chromosome-assigned whole genome shotgun (WGS) read libraries of alpha satellite. Each reference model provides an approximation of the true array sequence organization. Although the long-range repeat ordering is not expected to represent the true organization, the submissions are expected to provide a ...
This gene product is a highly conserved protein that facilitates centromere formation. It is a DNA-binding protein that is derived from transposases of the pogo DNA transposon family. It contains a helix-loop-helix DNA binding motif at the N-terminus, and a dimerization domain at the C-terminus. The DNA binding domain recognizes and binds a 17-bp sequence (CENP-B box) in the centromeric alpha satellite DNA. This protein is proposed to play an important role in the assembly of specific centromere structures in interphase nuclei and on mitotic chromosomes. It is also considered a major centromere autoantigen recognized by sera from patients with anti-centromere antibodies. [provided by RefSeq, Jul 2008 ...
Centromeres are the chromosomal regions that link DNA to the spindle during cell division, thus ensuring faithful segregation of genetic material. Proper centromere function is critical for eukaryotic life. Despite the fact that centromeres are essential for life, centromeric architecture is remarkably diverse. Moreover, centromeric DNA sequences and centromeric proteins evolve rapidly in diverse organisms. Despite this, the hallmark of many functional centromeres is the presence of a specialized centromeric H3 variant called CenH3. Despite being essential for chromosome segregation in most eukaryotes, CenH3 also evolves rapidly in plants and animals. I study the rapidly evolution of CenH3 in Drosophila. Specifically, I study instances in which CenH3 has duplicated and may have undergone subfunctionalization. I am intrigued by the possibility that these duplications may have arisen in response to genetic conflict such as centromere drive or due to intralocus antagonism. I use a variety of ...
The centromere-specific histone variant CENP-A (CID in Drosophila) is a structural and functional foundation for kinetochore formation and chromosome segregation. Here, we show that overexpressed CID is mislocalized into normally non-centromeric regions in Drosophila tissue culture cells and animals. Analysis of mitoses in living and fixed cells reveals that mitotic delays, anaphase bridges, chromosome fragmentation, and cell and organismal lethality are all direct consequences of CID mislocalization. In addition, proteins that are normally restricted to endogenous kinetochores assemble at a subset of ectopic CID incorporation regions. The presence of microtubule motors and binding proteins, spindle attachments, and aberrant chromosome morphologies demonstrate that these ectopic kinetochores are functional. We conclude that CID mislocalization promotes formation of ectopic centromeres and multicentric chromosomes, which causes chromosome missegregation, aneuploidy, and growth defects. Thus, CENP-A
DNA methylation is an epigenetically imposed mark of transcriptional repression that is essential for maintenance of chromatin structure and genomic stability. Genome-wide methylation patterns are mediated by the combined action of three DNA methyltransferases: DNMT1, DNMT3A and DNMT3B. Compelling links exist between DNMT3B and chromosome stability as emphasized by the mitotic defects that are a hallmark of ICF syndrome, a disease arising from germline mutations in DNMT3B. Centromeric and pericentromeric regions are essential for chromosome condensation and the fidelity of segregation. Centromere regions contain distinct epigenetic marks, including dense DNA hypermethylation, yet the mechanisms by which DNA methylation is targeted to these regions remains largely unknown. In the present study, we used a yeast two-hybrid screen and identified a novel interaction between DNMT3B and constitutive centromere protein CENP-C. CENP-C is itself essential for mitosis. We confirm this interaction in ...
Mitotic sister chromosomes individually attach to and harness the power of dynamic MT ends while maintaining an intercentromere elastic linkage that enables them to translocate jointly on the mitotic spindle and orient facing opposite spindle poles (Shelby et al., 1996). Robust MT attachments and proper orientation facing the opposite spindle poles maximizes the elastic pull on the sister centromeres and signals the cell that anaphase may safely commence. We have found that ectopically increasing the level of MCAK activity on centromeres decreases sister centromere tension, although not to the point that the spindle checkpoint is triggered. Conversely, decreased levels of MCAK on centromeres substantially increased tension across sister centromeres. Our data contradicts two other studies that suggest that the depletion of MCAK has no effect on tension (Ganem et al., 2005) or decreases tension (Kline-Smith et al., 2004). We believe that this discrepancy may be caused by the inclusion of ...
Our lab is interested in the epigenetic inheritance and organization of centromeres. The DNA sequence independent transmission of centromere identity through many cell generations is highly relevant for proper genome regulation and when perturbed can lead to genome instability and cellular malfunction. We use the fruit fly Drosophila melanogaster and human cells as a model organism to address the following questions: How is the epigenetic identity of centromeres regulated?. Centromeres are found at the primary constriction of chromosomes in mitosis where they remain connected before cell division. This structure is essential for an equivalent chromosomes distribution to the daughter cells. The centromere specific histone H3-variant CENP-AcenH3 is essential for kinetochore formation and centromere function. We have previously established a biosynthetic approach to target dCENP-AcenH3 to specific non-centromeric sequences such as the Lac Operator and follow the formation of functional ...
Stringent regulation of cellular levels of evolutionarily conserved centromeric histone H3 variant (CENP-A in humans, CID in flies, Cse4 in yeast) prevents its mislocalization to non-centromeric chromatin. Overexpression and mislocalization of CENP-A has been observed in cancers and leads to aneuploidy in yeast, flies, and human cells. Ubiquitin-mediated proteolysis of Cse4 by E3 ligases such as Psh1 and Sumo-Targeted Ubiquitin Ligase (STUbL) Slx5 prevent mislocalization of Cse4. Previously, we identified Siz1 and Siz2 as the major E3 ligases for sumoylation of Cse4. In this study, we have identified lysine 65 (K65) in Cse4 as a site that regulates sumoylation and ubiquitin-mediated proteolysis of Cse4 by Slx5. Strains expressing cse4 K65R exhibit reduced levels of sumoylated and ubiquitinated Cse4 in vivo. Furthermore, co-immunoprecipitation experiments reveal reduced interaction of cse4 K65R with Slx5, leading to increased stability and mislocalization of cse4 K65R under normal physiological ...
KAT7/HBO1/MYST2 Regulates CENP-A Chromatin Assembly by Antagonizing Suv39h1-Mediated Centromere InactivationKAT7/HBO1/MYST2 Regulates CENP-A Chromatin Assembly by Antagonizing Suv39h1-Mediated Centromere Inactivation ...
Author Summary The centromere is a chromosome domain essential for the correct partitioning of chromosomes during mitotic and meiotic cell divisions. The characterization of the centromeric proteins and their sequential assembly have been extensively studied in mammalian mitosis, since defective chromosome segregation is associated with birth defects and cancer. However, few studies have analyzed the centromere assembly during meiosis, a special cell division leading to the production of haploid gametes. Here, we analyze the sequence of loading of several centromeric and kinetochoric proteins during male mouse meiosis. We show that during both meiotic divisions, the proteins of the chromosomal passenger complex Borealin, INCENP, and Aurora-B load sequentially to the inner centromere before Shugoshin 2 and MCAK. The outer kinetochore proteins BubR1 and CENP-E are the last ones to be assembled. We also demonstrate, using a knockout mouse for Sgol2, that the inner centromeric protein Shugoshin 2 is
Inner centromere protein is a protein that in humans is encoded by the INCENP gene.[5][6][7] In mammalian cells, two broad groups of centromere-interacting proteins have been described: constitutively binding centromere proteins and passenger (or transiently interacting) proteins.[8] The constitutive proteins include CENPA (centromere protein A), CENPB, CENPC1, and CENPD. The term passenger proteins encompasses a broad collection of proteins that localize to the centromere during specific stages of the cell cycle.[9] These include CENPE; MCAK; KID; cytoplasmic dynein (e.g., DYNC1H1); CliPs (e.g. CLIP1); and CENPF/mitosin (CENPF). The inner centromere proteins (INCENPs),[5] the initial members of the passenger protein group, display a broad localization along chromosomes in the early stages of mitosis but gradually become concentrated at centromeres as the cell cycle progresses into mid-metaphase. During telophase, the proteins are located within the midbody in the intercellular bridge, where ...
This organism was chosen because it has epigenetically defined "regional centromeres" whose chromatin and protein compositions are similar to those of their human counterparts, to identify factors responsible for the replacement of histone H3 with CENP-A at centromeres.. In this report, the KAIST research group systematically analyzed the roles of the ATP-dependent chromatin-remodelers in the centromeric chromatin assembly of fission yeast as they serve as strong candidates for such factors ...
Centromeres are specialized chromosomal domains which are composed of centromeric DNA, often enriched in satellite repeats, and a large protein complex, the "kinetochore". Proper assembly of the kinetochore complex is a prerequisite for the correct segregation of chromosomes during mitotic and meiotic divisions and, consequently, for genome stability in all eukaryotic organisms. Deposition of the centromeric histone H3 variant CenH3 at the centromeric region is a prerequisite for correct assembly and function of the kinetochore complex in most eukaryotes. CenH3 deposition depends on cenH3 assembly factors, like KNL2 (Lermontova et al., 2013; Sandmann et al., 2017), chaperones (e.g. NASPSIM3, Le Goff et al., 2020), transcription of the centromeric repeats and the epigenetic status of centromeric chromatin. Specific manipulation of the CenH3 assembly factor KNL2 yielded double haploids in Arabidopsis thaliana (I. Lermontova, WO2017/067714). The production of double haploids enables a shortcut to ...
As the spindle fiber attachment region of the chromosome, the centromere has been investigated in a variety of contexts. Here, we will review current knowledge about this unique chromosomal region and its relevance for proper cell division, speciation, and disease. Understanding the three-dimensional organization of centromeres in normal and turner cells is just beginning to emerge. Multidisciplinary research will allow for new insights into its normal and aberrant nuclear organization and may allow for new therapeutic interventions that target events linked to centromere function and cell division ...
Following a close collaboration with the Chan lab and the demise of Simon Chan in the Summer of 2012, we have assimilated Chan lab researchers working on different aspects of centromeric function and its epigenetic determination. We are investigating the structural features, evolutionary constraints, and mechanisms that determine the interaction of centromeric histone H3 (CENH3) with the centromere and its instability in outcrosses resulting in parent-specific genome elimination. In collaboration with the Korf lab, we are investigating the mechanisms of extreme chromosome fragmentation and reassembly that are associated to chromosome elimination. ...
Following a close collaboration with the Chan lab and the demise of Simon Chan in the Summer of 2012, we have assimilated Chan lab researchers working on different aspects of centromeric function and its epigenetic determination. We are investigating the structural features, evolutionary constraints, and mechanisms that determine the interaction of centromeric histone H3 (CENH3) with the centromere and its instability in outcrosses resulting in parent-specific genome elimination. We are investigating the mechanisms of extreme chromosome fragmentation and reassembly that are associated to chromosome elimination. ...
Alignment of the centromere regions of all sixteen chromosomes. The regions include the Centromere DNA Elements I II and III (CDEI, CDEII and CDEIII). The conserved bases in all centromeres are marked in magenta. The regions with less conserved residues of CDEI and CDEIII are marked in green. The CDEII region which contains more than 90% AT residues has been left white. The multiple sequence alignment was created with PILEUP ...
GF ID Scm3 #=GF AC PF10384.8 #=GF DE Centromere protein Scm3 #=GF AU Mistry J, Wood V #=GF SE Pfam-B_19394 (release 21.0) #=GF GA 24.30 24.30; #=GF TC 24.60 24.40; #=GF NC 24.20 24.00; #=GF BM hmmbuild HMM.ann SEED.ann #=GF SM hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq #=GF TP Family #=GF RN [1] #=GF RM 17548816 #=GF RT Scm3, an essential Saccharomyces cerevisiae centromere protein #=GF RT required for G2/M progression and Cse4 localization. #=GF RA Stoler S, Rogers K, Weitze S, Morey L, Fitzgerald-Hayes M, Baker #=GF RA RE; #=GF RL Proc Natl Acad Sci U S A. 2007;104:10571-10576. #=GF RN [2] #=GF RM 17704645 #=GF RT Domain Architectures of the Scm3p Protein Provide Insights into #=GF RT Centromere Function and Evolution. #=GF RA Aravind L, Iyer LM, Wu C; #=GF RL Cell Cycle. 2007; [Epub ahead of print] #=GF RN [3] #=GF RM 19563746 #=GF RT Common ancestry of the CENP-A chaperones Scm3 and HJURP. #=GF RA Sanchez-Pulido L, Pidoux AL, Ponting CP, Allshire RC; #=GF RL Cell. 2009;137:1173-1174. ...
The localization of yeast centromeres and the 2-μm circle. Centromeres cluster close to the spindle pole body in late G1, but do not localize to the extreme nu
Centromeres are specialized chromatin structures that are required for cell division. The composition of these regions is complex, as they are made up of a series of tandem repeats that are arranged into nearly identical multi-megabase arrays. The size and repetitive nature of these regions mean they are typically not represented in reference assemblies. The Human Genome Project (HGP) employed a clone based strategy (largely BAC clones) to produce the reference assembly, but cloning centromere sequences generally requires special effort, and isnt readily applicable to all human centromeres (see Kouprina et al., 2003 for one such effort). With the recent widespread adoption of whole genome sequencing (WGS), there are clearly alpha-satellite sequences in the reads produced, but assembling these sequences into faithful representations of centromeres using standard techniques is impossible due to the repetitive nature of these sequences. In all previous versions of the human reference assembly, the ...
Centromeres are specialized chromatin structures that are required for cell division. The composition of these regions is complex, as they are made up of a series of tandem repeats that are arranged into nearly identical multi-megabase arrays. The size and repetitive nature of these regions mean they are typically not represented in reference assemblies. The Human Genome Project (HGP) employed a clone based strategy (largely BAC clones) to produce the reference assembly, but cloning centromere sequences generally requires special effort, and isnt readily applicable to all human centromeres (see Kouprina et al., 2003 for one such effort). With the recent widespread adoption of whole genome sequencing (WGS), there are clearly alpha-satellite sequences in the reads produced, but assembling these sequences into faithful representations of centromeres using standard techniques is impossible due to the repetitive nature of these sequences. In all previous versions of the human reference assembly, the ...
1. Steiner FA, Henikoff S. Diversity in the organization of centromeric chromatin. Current Opinion in Genetics & Development. 2015;31(0):28-35. doi: http://dx.doi.org/10.1016/j.gde.2015.03.010.. 2. Fukagawa T, Earnshaw William C. The Centromere: Chromatin Foundation for the Kinetochore Machinery. Developmental Cell. 30(5):496-508. doi: 10.1016/j.devcel.2014.08.016 25203206. 3. Cheeseman IM. The Kinetochore. Cold Spring Harbor Perspectives in Biology. 2014;6(7). doi: 10.1101/cshperspect.a015826. 4. Duro E, Marston AL. From equator to pole: splitting chromosomes in mitosis and meiosis. Genes & Development. 2015;29(2):109-22. doi: 10.1101/gad.255554.114. 5. Allshire RC, Karpen GH. Epigenetic regulation of centromeric chromatin: old dogs, new tricks? Nat Rev Genet. 2008;9(12):923-37. doi: 10.1038/nrg2466 19002142. 6. Sekulic N, Black BE. Molecular underpinnings of centromere identity and maintenance. Trends in Biochemical Sciences. 37(6):220-9. doi: 10.1016/j.tibs.2012.01.003 22410197. 7. Palmer DK, ...
Our research program is focused on the important basic question of how chromosomes are segregated during cell division to ensure the complete and accurate inheritance of the genome. Chromosome instability is a hallmark of cancer and can drive tumorigenesis. Therefore, how centromere specification is controlled is a basic biological question with great therapeutic potential. Centromeres are specified by the incorporation of a histone variant CENP-A, and stable inheritance of this locus is control...[Read full text]Our research program is focused on the important basic question of how chromosomes are segregated during cell division to ensure the complete and accurate inheritance of the genome. Chromosome instability is a hallmark of cancer and can drive tumorigenesis. Therefore, how centromere specification is controlled is a basic biological question with great therapeutic potential. Centromeres are specified by the incorporation of a histone variant CENP-A, and stable inheritance of this locus ...
TY - JOUR. T1 - Probing the architecture of a simple kinetochore using DNA-protein crosslinking. AU - Espelin, Christopher W.. AU - Kaplan, Kenneth B.. AU - Sorger, Peter K.. PY - 1997/12/15. Y1 - 1997/12/15. N2 - In budding yeast, accurate chromosome segregation requires that one and only one kinetochore assemble per chromosome. In this paper, we report the use of DNA-protein crosslinking and nondenaturing gel analysis to study the structure of CBF3, a four-protein complex that binds to the essential CDEIII region of Saccharomyces cerevisiae centromeres. We find that three subunits of CBF3 are in direct contact with CDEIII over a region of DNA that spans 80 bp. A highly asymmetric core complex containing p58(CTF13) p64(CEP3) and p110(NDC10) in direct contact with DNA forms at the genetically defined center of CDEIII. This core complex spans ~56 bp of CEN3. An extended complex comprising the core complex and additional DNA-bound p110(NDC10) also forms. It spans ~80 bp of DNA. CBF3 makes ...
In this diagram o a duplicatit chromosome, (2) identifies the centromere-the region that jyns the twa sister chromatids, or each hauf o the chromosome. In prophase o mitosis, specialised regions on centromeres cried kinetochores attach chromosomes tae spindle fibers ...
The centromere is the structure at the center of every X-shaped chromosome, where cells attached the long, thin spindles that pull the two copies of DNA apart during cell division. A new technique makes it much easier to study centromeres, and look for links to conditions such as Down syndrome.
Centromere B Ab ELISA Kit is an indirect solid phase enzyme immunoassay for the quantitative measurement of IgG class autoantibodies against Centromere B in human serum or plasma. (KA1275) - Products - Abnova
Chromosomes can be classified based on the following except ____. a) centromere location b) centromere size c) number of centromeres d) centromere duration
Article source: http://theworldseeds.cn/index.php?p=152804 (Translated by Google Translate) The centromere and its surroundings are the fastest-evolving and…
CENPP is a subunit of a CENPH (MIM 605607)-CENPI (MIM 300065)-associated centromeric complex that targets CENPA (MIM;117139) to centromeres and is required for proper kinetochore function and mitotic progression (Okada et al., 2006;(PubMed 16622420 ...
We study the spectrum and mechanisms of telomere function. Recent highlights include the discovery of a mode by which telomerase-negative cells can use generic heterochromatin to protect ends. We have also expanded the telomeric repertoire, finding that telomeres control meiotic spindle formation and centromere assembly; these principles apply to proliferating cells as well, as centromeres control the decision to mount mitotic spindle assembly.. Keywords: Telomeres / Centromeres / DNA damage response / fission yeast / meiosis / chromatin & nuclear organization. Subject area(s): Cell Cycle , Chromatin & Transcription , Genome Stability & Dynamics. ...