Dicentric chromosomes: unique models to study centromere function and inactivation

Stimpson, Kaitlin M.; Matheny, Justyne E.; Sullivan, Beth A.

doi:10.1007/s10577-012-9302-3

Cited by 91 publications

(101 citation statements)

References 53 publications

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“…In both patients, there is a pseudodicentric chromosome with inactivation of the Y centromere, resulting in a functionally monocentric chromosome. The literature shows that functionally monocentric chromosomes are usually stable and segregate normally during cell division [Stimpson et al, 2012].…”

Section: Discussionmentioning

confidence: 99%

Miller-Dieker Syndrome due to a 5.5-Mb 17p Deletion in a 17;Y Pseudodicentric Chromosome

Bellucco

Nunes²,

Colovati³

et al. 2017

Cytogenet Genome Res

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Miller-Dieker syndrome (MDS) is a contiguous gene deletion syndrome in which almost all patients present de novo 17p13.3 deletions. We report on a male infant with MDS and an unusual unbalanced translocation involving chromosomes Y and 17 that resulted in a large 5.5-Mb 17pterp13.2 deletion and a karyotype with 45 chromosomes. Apart from the deletion of the MDS critical region, the deletion of additional distal genes seemed to have no major influence on the patient's phenotype, since he did not show any unusual clinical findings that are not commonly described in MDS patients.

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Section: Discussionmentioning

confidence: 99%

Miller-Dieker Syndrome due to a 5.5-Mb 17p Deletion in a 17;Y Pseudodicentric Chromosome

Bellucco

Nunes²,

Colovati³

et al. 2017

Cytogenet Genome Res

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“…Typically, dicentric chromosomes are thought to be generated from arm breakage or shortening of telomeres, and consecutive rearrangements (Frias et al 2012). These chromosomes are unstable due to the presence of two active centromeric regions that may attach to opposite spindle poles, resulting in chromosome bridges and breakage in anaphase (Stimpson et al 2012). In rare instances, dicentric chromosomes can stabilize due to the inactivation of one of the two centromeres by deletion or by epigenetic silencing (Earnshaw and Migeon 1985;Merry et al 1985;Earnshaw and Cooke 1989;Stimpson et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Using human artificial chromosomes to study centromere assembly and function

et al. 2017

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Abstract:Centromeres are the site of assembly of the kinetochore, which directs chromosome segregation during cell division. Active centromeres are characterized by the presence of nucleosomes containing CENP-A and a specific chromatin environment that resembles that of active genes. Recent work using Human Artificial Chromosomes (HAC) sheds light on the fine balance of different histone post-translational modifications and transcription that exists at centromeres for kinetochore assembly and maintenance. Here, we review the use of HAC technology to understand centromere assembly and function. We put particular emphasis on studies using the alphoidtetO HAC, whose centromere can be specifically modified for epigenetic engineering studies. Author Comments:We suggest Professor Erich Nigg as an Editor (not found in the "Request Editor" list), who invited us to write this review.Response to Reviewers: Comments for the Author:Reviewer #1: Since there has been significant progress over the last few years with regards to HAC technology, particularly with alphoidtetO HACs, a review on this topic would be welcomed in the field, especially by these authors, who are world experts on Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporationthis topic. The review is mostly satisfying, but I would suggest two areas where the authors would be well served to make additions/changes to avoid disappointing readers hoping for more focus/organization/clarity. First, since the goal of this review is to "review the use of HAC technology to understand centromere assembly and function", it would be especially helpful if the authors summarized the evolution of HAC technology and the findings that came from targeting different tetR fusion proteins to the alphoidtetO HACs (probably most effectively in a table or schematic).We thank the reviewer for the thoughtful review of our MS. Following the reviewer´s advice, a table has been added explaining the findings that came from the alphoidtetO HAC studies in a timeline manner (Table 1).Second, more discussion on the pitfalls of current HACs would be desirable (currently only a couple sentences is mentioned in the future directions). From how it is written they sound so great that a reader would probably wonder why they are not used more widely in the research lab and/or clinic. There are problems with them, and it would be more clear and interesting, in my opinion, if more of the problems were laid out/challenges addressed.A description of limitations of the HAC technology have been added in the text, first limitations for HAC clinical use (p. 8-9) and additional limitations that should be overcome in the final remarks (p. 23). Some other changes that I'd suggest:1. It's confusing to refer to the same DNA as "alpha satellite", "α-satellite", and "alpha-satellite" throughout the review (most notably in the first two lines of the second paragraph). Why not just refer to it as "α-satellite" DNA?We changed the term to α-satellite DNA throughout the text to maintain consist...

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“…Most of our current understanding of how dicentrics are stabilized comes from studies of artificially-induced or engineered dicentric chromosomes in yeast (Pobiega and Marcand 2010; Sato et al 2012), fruit flies (Agudo et al 2000), and human cell lines (Higgins et al 1999; Higgins et al 2005; Stimpson et al 2010; Stimpson et al 2012), as well as a few examples of dicentric chromosomes in found in plants (Sears and Câmara 1952; Han et al 2006; Zhang et al 2010; Gao et al 2011; Koo et al 2011; Liu et al 2015) and human patients (Therman et al 1989; Maraschio et al 1990; Fisher et al 1997; Page and Schaffer 1998; Sullivan and Willard 1998; Lange et al 2009; Stimpson et al 2012). In some engineered systems, the dicentric chromosome can simply break in order to re-establish monocentric chromosomes (Pobiega and Marcand 2010; Sato et al 2012).…”

Section: Introductionmentioning

confidence: 99%

“…In other engineered or patient-derived dicentrics, chromosome fusions can be stably inherited because the two centromeres on a fusion chromosome are close enough to each other to act as a single centromere (Koshland et al 1987; Page and Shaffer 1998; Sullivan and Willard 1998; Higgins et al 1999; Lange et al 2009). However, distance between the centromeres does not fully explain the stable maintenance of dicentric chromosomes, and in many cases, there is inactivation of one of the centromeres to re-establish functionally monocentric chromosomes (Stimpson et al 2012). Centromere inactivation can either occur by genetic or epigenetic inactivation of one centromere.…”

Section: Introductionmentioning

confidence: 99%

Centromere inactivation on a neo-Y fusion chromosome in threespine stickleback fish

Cech

Peichel

2016

Chromosome Res

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Having one and only one centromere per chromosome is essential for proper chromosome segregation during both mitosis and meiosis. Chromosomes containing two centromeres are known as dicentric and often mis-segregate during cell division, resulting in aneuploidy or chromosome breakage. Dicentric chromosome can be stabilized by centromere inactivation, a process which re-establishes monocentric chromosomes. However, little is known about this process in naturally occurring dicentric chromosomes. Using a combination of fluorescence in situ hybridization (FISH) and immunoflourescence combined with FISH (IF-FISH) on metaphase chromosome spreads, we demonstrate that centromere inactivation has evolved on a neo-Y chromosome fusion in the Japan Sea threespine stickleback fish (Gasterosteus nipponicus). We found that the centromere derived from the ancestral Y chromosome has been inactivated. Our data further suggest that there have been genetic changes to this centromere in the two million years since the formation of the neo-Y chromosome, but it remains unclear whether these genetic changes are a cause or consequence of centromere inactivation.

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Dicentric chromosomes: unique models to study centromere function and inactivation

Cited by 91 publications

References 53 publications

Miller-Dieker Syndrome due to a 5.5-Mb 17p Deletion in a 17;Y Pseudodicentric Chromosome

Miller-Dieker Syndrome due to a 5.5-Mb 17p Deletion in a 17;Y Pseudodicentric Chromosome

Using human artificial chromosomes to study centromere assembly and function

Centromere inactivation on a neo-Y fusion chromosome in threespine stickleback fish

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