Localization of motor-related proteins and associated complexes to active, but not inactive, centromeres

Faulkner, Nicole; Vig, Baldev K.; Echeverri, Christophe de Jesus; Wordeman, Linda; Vallee, Richard B.

doi:10.1093/hmg/7.4.671

Cited by 39 publications

(26 citation statements)

References 49 publications

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“…Despite this, only one of the two identical sites forms an active neocentromere. This situation parallels that found in pseudo-dicentric or pseudo-multicentric chromosomes arising from translocation events where only one centromere remains active [Faulkner et al, 1998;Page et al, 1995;Sullivan et al, 1995]. Presumably, the same mechanism that prevents more than one centromere on these chromosomes from becoming active operates in the inv dup(20) case to prevent both arms of the inverted duplication from forming neocentromeres.…”

Section: Discussionsupporting

confidence: 69%

“…The chromosome is present in 100% of cells examined from blood lymphocytes and transformed lymphoblast and fibroblast cell cultures, indicating faithful chromosome segregation. Immunofluorescence using antibodies against centromere proteins CENP-A, CENP-C, CENP-E, CENP-F, and INCENP, all considered as markers for active centromeres [Chan et al, 1998;Faulkner et al, 1998;Kalitsis et al, 1998;Mackay et al, 1998;Sullivan et al, 1994;Sullivan and Schwartz, 1995;Thrower et al, 1995], provided further evidence for the presence of a functional centromere on the constricted arm of the inv dup(20p) chromosome. Two lines of evidence suggest the formation of this functional centromere through the activation of a neocentromere on the inv dup(20p) chromosome.…”

Section: Discussionmentioning

confidence: 99%

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Trisomy 20p resulting from inverted duplication and neocentromere formation

et al. 1999

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Normal human centromeres contain large tandem arrays of alpha-satellite DNA of varying composition and complexity. However, a new class of mitotically stable marker chromosomes which contain neocentromeres formed from genomic regions previously devoid of centromere activity was described recently. These neocentromeres are fully functional yet lack the repeat sequences traditionally associated with normal centromere function. We report here a supernumerary marker chromosome derived from the short arm of chromosome 20 in a patient with manifestations of dup(20p) syndrome. Detailed cytogenetic, FISH, and polymorphic microsatellite analyses indicate the de novo formation of the marker chromosome during meiosis or early postzygotically, involving an initial chromosome breakage at 20p11.2, followed by an inverted duplication of the distal 20p segment due to rejoining of sister chromatids and the activation of a neocentromere within 20p12. This inv dup(20p) marker chromosome lacks detectable centromeric alpha-satellite and pericentric satellite III sequences, or centromere protein CENP-B. Functional activity of the neocentromere is evidenced by its association with 5 different, functionally critical centromere proteins: CENP-A, CENP-C, CENP-E, CENP-F, and INCENP. Formation of a neocentromere on human chromosome 20 has not been reported previously and in this context represents a new mechanism for the origin of dup(20p) syndrome.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Trisomy 20p resulting from inverted duplication and neocentromere formation

et al. 1999

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“…13). An alternative possibility is that after integration, one centromere sequence is silenced, which is one mechanism observed to prevent instability in dicentric chromosomes (60,61). However, our observation of only one centromere-like DNA sequence per chromosome based on ChIP-seq experiments would suggest that this is not the case, at least in recent diatom evolutionary history.…”

Section: Discussionmentioning

confidence: 77%

Diatom centromeres suggest a mechanism for nuclear DNA acquisition

Diner

Noddings

Lian

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Centromeres are essential for cell division and growth in all eukaryotes, and knowledge of their sequence and structure guides the development of artificial chromosomes for functional cellular biology studies. Centromeric proteins are conserved among eukaryotes; however, centromeric DNA sequences are highly variable. We combined forward and reverse genetic approaches with chromatin immunoprecipitation to identify centromeres of the model diatom Phaeodactylum tricornutum. We observed 25 unique centromere sequences typically occurring once per chromosome, a finding that helps to resolve nuclear genome organization and indicates monocentric regional centromeres. Diatom centromere sequences contain low-GC content regions but lack repeats or other conserved sequence features. Native and foreign sequences with similar GC content to P. tricornutum centromeres can maintain episomes and recruit the diatom centromeric histone protein CENH3, suggesting nonnative sequences can also function as diatom centromeres. Thus, simple sequence requirements may enable DNA from foreign sources to persist in the nucleus as extrachromosomal episomes, revealing a potential mechanism for organellar and foreign DNA acquisition.diatom | Phaeodactylum tricornutum | episome | centromere | CENH3

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“…Direct proof of centromere function in the low-alphoid chromosomes has come from immunocytochemical studies using antibodies against two functionally important centromere proteins, CENP-C and CENP-E. CENP-C has been reported to regulate kinetochore structural integrity (Tomkiel et al 1994) and to be essential for mitosis as evident from a lethal phenotype in gene knockout studies (Fukagawa and Brown 1997;Kalitsis et al 1998), whereas CENP-E is a molecular motor that has been shown to move chromosomes along microtubules (Thrower et al 1995). The importance of CENP-C and CENP-E in centromere function is further suggested by the observation that these proteins are found on active, but not inactive, centromeres in dicentric or multicentric chromosomes (Earnshaw et al 1989;Page et al 1995;Sullivan and Schwartz 1995;Faulkner et al 1998). Thus, the detection of both of these antigens on each of the lowalphoid centromere cases has provided direct support for the functional integrity of these centromeres.…”

Section: Wwwgenomeorgmentioning

confidence: 99%

Extreme Reduction of Chromosome-Specific α-Satellite Array Is Unusually Common in Human Chromosome 21

Liao²,

Rocchi³

et al. 1999

Genome Res.

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Human centromeres contain large arrays of ␣-satellite DNA that are thought to provide centromere function. The arrays show size and sequence variation, but the extent to which extremely low levels of this DNA can occur on normal centromeres is unclear. Using a set of chromosome-specific ␣-satellite probes for each of the human chromosomes, we performed interphase fluorescence in situ hybridization (FISH) in a population-screening study. Our results demonstrate that extreme reduction of chromosome-specific ␣ satellite is unusually common in chromosome 21 (screened with the ␣RI probe), with a prevalence of 3.70%, compared to Յ0.12% for each of chromosomes 13 and 17, and 0% for the other chromosomes. No analphoid centromere was identified in >17,000 morphologically normal chromosomes studied. All of the low-alphoid centromeres are fully functional as indicated by their mitotic stability and binding to centromere proteins CENP-B, CENP-C, and CENP-E. Sensitive metaphase FISH analysis of the low-alphoid chromosome 21 centromeres established the presence of residual ␣RI as well as other non-␣RI ␣-satellite DNA suggesting that centromere function may be provided by (1) the residual ␣RI DNA, (2) other non-␣RI ␣-satellite sequences, (3) a combination of 1 and 2, or (4) an activated neocentromere DNA. The low-alphoid centromeres, in particular those of chromosome 21, should provide unique opportunities for the study of the evolution and the minimal DNA requirement of the human centromere.

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Localization of motor-related proteins and associated complexes to active, but not inactive, centromeres

Cited by 39 publications

References 49 publications

Trisomy 20p resulting from inverted duplication and neocentromere formation

Trisomy 20p resulting from inverted duplication and neocentromere formation

Diatom centromeres suggest a mechanism for nuclear DNA acquisition

Extreme Reduction of Chromosome-Specific α-Satellite Array Is Unusually Common in Human Chromosome 21

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