Article

Dicentric chromosomes: Unique models to study centromere function and inactivation

Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA.
Chromosome Research (Impact Factor: 2.69). 07/2012; 20(5):595-605. DOI: 10.1007/s10577-012-9302-3
Source: PubMed

ABSTRACT Dicentric chromosomes are products of genome rearrangement that place two centromeres on the same chromosome. Depending on the organism, dicentric stability varies after formation. In humans, dicentrics occur naturally in a substantial portion of the population and usually segregate successfully in mitosis and meiosis. Their stability has been attributed to inactivation of one of the two centromeres, creating a functionally monocentric chromosome that can segregate normally during cell division. The molecular basis for centromere inactivation is not well understood, although studies in model organisms and in humans suggest that genomic and epigenetic mechanisms can be involved. Furthermore, constitutional dicentric chromosomes ascertained in patients presumably represent the most stable chromosomes, so the spectrum of dicentric fates, if it exists, is not entirely clear. Studies of engineered or induced dicentrics in budding yeast and plants have provided significant insight into the fate of dicentric chromosomes. And, more recently, studies have shown that dicentrics in humans can also undergo multiple fates after formation. Here, we discuss current experimental evidence from various organisms that has deepened our understanding of dicentric behavior and the intriguingly complex process of centromere inactivation.

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    • "Indeed, in humans some centromere inactivations were followed by a partial deletion of the centromere-specific a-satellite associated with CENP-A, which are important for the kinetochore assembly (Stimpson et al., 2010). In budding and fission yeast, originally dicentric chromosomes were stabilized by physical deletion of one centromere (Sato et al., 2012; Stimpson et al., 2012). Data on the recombinational loss of centromeric sequences in plants are scarce. "
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    ABSTRACT: Functional centromeres, ensuring regular chromosome segregation in mitosis and meiosis, are a prerequisite for the evolutionary success of pre‐existing and new chromosome variants. The rapid progress in plant comparative genomics and cytogenetics brings new insights into the evolutionary fate of centromeres and mechanisms of chromosome number reduction (descending dysploidy). Centromere loss and relocation in chromosome regions with otherwise conserved collinearity can be explained by conventional mechanisms of chromosome rearrangements or, as newly available phylogenomic and cytogenomic data suggest, by centromere inactivation through epigenetic chromatin modifications and/or intra‐ and inter‐chromosomal recombination.
    New Phytologist 09/2014; 203(4). DOI:10.1111/nph.12885 · 7.67 Impact Factor
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    • "In addition, studies in mammalian cells and plants have suggested that, in dicentric chromosomes, one centromere can be more prone to inactivation than the other (Sullivan and Schwartz 1995; Lamb et al. 2008; Stimpson et al. 2012); centromere inactivation in mammals involves both intracentromeric structural changes (deletions) and epigenetic mechanisms (Stimpson et al. 2010). "
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    ABSTRACT: Dicentric chromosomes undergo breakage in mitosis, resulting in chromosome deletions, duplications, and translocations. In this study, we map chromosome break sites of dicentrics in Saccharomyces cerevisiae by a mitotic recombination assay. The assay uses a diploid strain in which one homolog has a conditional centromere in addition to a wild-type centromere, and the other homolog has only the wild-type centromere; the conditional centromere is inactive when cells are grown in galactose and is activated when the cells are switched to glucose. In addition, the two homologs are distinguishable by multiple single-nucleotide polymorphisms (SNPs). Under conditions in which the conditional centromere is activated, the functionally dicentric chromosome undergoes double-stranded DNA breaks (DSBs) that can be repaired by mitotic recombination with the homolog. Such recombination events often lead to loss of heterozygosity (LOH) of SNPs that are centromere-distal to the crossover. Using a PCR-based assay, we determined the position of LOH in multiple independent recombination events to a resolution of about 4 kb. This analysis shows that dicentric chromosomes have recombination breakpoints that are broadly distributed between the two centromeres, although there is a clustering of breakpoints within 10 kb of the conditional centromere.
    Genetics 02/2013; 194(1). DOI:10.1534/genetics.113.150144 · 4.87 Impact Factor
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    • "These heterodicentric chromosomes have two alpha satellite sequences on the same chromosome which leads to a high risk of attachment of the same chromatid to the mitotic spindle from opposite poles and also in the formation of Anaphase Bridge during cell division. But in humans, dicentrics occur naturally in a substantial portion of the population and usually segregate successfully in mitosis and meiosis [8]. Their stability has been attributed to inactivation of one of the two centromeres, creating a functionally monocentric chromosome that can segregate normally during cell division or when the centromeres are very close to each other and form only one heterochromatic block [9]. "
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    ABSTRACT: We report a 16-year-old girl who presented with short stature and amenorrhea. Initially the cytogenetic analysis showed the presence of a mosaic non-Robertsonian dicentric chromosome involving chromosomes 14 and 19. Subsequent molecular cytogenetic analysis by fluorescence in situ hybridization (FISH) using whole chromosome paints, centromeric probes, as well as gene specific probes confirmed the dicentric nature of the derivative chromosome and indicated that the rearrangement involved the short arms of both of these chromosomes. Furthermore, we also determined that the chromosome 19p13.3 breakpoint occurred within the terminal 1 Mb region. This is the first report of a mosaic non-Robertsonian dicentric chromosome involving chromosomes 14 and 19 with the karyotype determined as 45,XX,dic(14;19)(p11.2;p13.3)[35]/46,XX[15], and we suggest that the chromosome rearrangement could be the cause of clinical phenotype.
    11/2012; 2012:212065. DOI:10.1155/2012/212065
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