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Molecular Insights into Centromere Assembly and Dysfunction
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Molecular Insights into Centromere Assembly and Dysfunction

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (30 July 2021) | Viewed by 3185

Special Issue Editors

Prof. Aldo Di Leonardo

E-Mail Website
Guest Editor
University of Palermo, 90133 Palermo, Italy
Interests: genetics; chromosomal instability; aneuploidy; cell cycle; cancer genetics;
Dr. Viviana Barra

E-Mail Website
Guest Editor
University of Palermo, 90133 Palermo, Italy
Interests: cancer research; epigenetics; medical genetics; DNA methylation; chromosomes; molecular genetics;

Special Issue Information

Dear Colleagues,

We would like to invite you to contribute to this Special Issue of Genes titled “Molecular Insights into Centromere Assembly and Dysfunction”.

The aim of this Special Issue is to collect reviews and original research articles that advance our understanding of the mechanisms responsible for centromere assembly and dysfunction. We welcome author contributions highlighting novel findings on the assembly of the centromere, its (epi)genetic regulation, the molecular mechanisms operating at the centromere, and causes of centrosome dysfunction/malfunction associated with chromosome stability and their roles in human diseases. Centromeres are unique chromosome loci characterized by the binding of a special histone H3 variant known as CENP-A in vertebrates, Cse4 in Saccharomyces cerevisiae, Cid in Drosophila melanogaster, and HCP-3 in Caenorhabditis elegans. Here, the kinetochore complex adheres and sister chromatids are held together ensuring the faithful segregation in mitosis and meiosis. Hence, the correct assembly (protein composition, (epi)genetic background, integrity, localization, topology, and regulation) of the centromere is essential for the maintenance of chromosome (genome) stability. Unsurprisingly, therefore, alterations of centromeres, such as increased expression and mislocalization of CENP-A, have been reported in human diseases including cancer. This evidence highlights the importance of centromere studies for human health.

Prof. Aldo Di Leonardo
Dr. Viviana Barra
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Centromere
  • Kinetochore
  • Centromeric proteins
  • Genomic instability
  • Epigenetics
  • Chromosome
  • Repetitive DNA
  • Centromere misregulation

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Published Papers (1 paper)

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Research

12 pages, 1377 KiB  
Article
Transcriptomic Changes Following Partial Depletion of CENP-E in Normal Human Fibroblasts
by Danilo Cilluffo, Roberta Flavia Chiavetta, Serena Bivona, Flavia Contino, Claudia Coronnello, Salvatore Feo, Aldo Di Leonardo and Viviana Barra
Genes 2021, 12(9), 1322; https://doi.org/10.3390/genes12091322 - 26 Aug 2021
Cited by 3 | Viewed by 2701
Abstract
The centromere is a fundamental chromosome structure in which the macro-molecular kinetochore assembles and is bound by spindle microtubules, allowing the segregation of sister chromatids during mitosis. Any alterations in kinetochore assembly or functioning or kinetochore–microtubule attachments jeopardize chromosome stability, leading to aneuploidy, [...] Read more.
The centromere is a fundamental chromosome structure in which the macro-molecular kinetochore assembles and is bound by spindle microtubules, allowing the segregation of sister chromatids during mitosis. Any alterations in kinetochore assembly or functioning or kinetochore–microtubule attachments jeopardize chromosome stability, leading to aneuploidy, a common feature of cancer cells. The spindle assembly checkpoint (SAC) supervises this process, ensuring a faithful segregation of chromosomes. CENP-E is both a protein of the kinetochore and a crucial component of the SAC required for kinetochore–microtubule capture and stable attachment, as well as congression of chromosomes to the metaphase plate. As the function of CENP-E is restricted to mitosis, its haploinsufficiency has been used to study the induced cell aneuploidy; however, the gene expression profile triggered by CENP-E reduction in normal cells has never been explored. To fill this gap, here we investigated whether a gene network exists that is associated with an siRNA-induced 50% reduction in CENP-E and consequent aneuploidy. Gene expression microarray analyses were performed at early and late timepoints after transfection. Initially, cell cycle regulation and stress response pathways were downregulated, while afterwards pathways involved in epithelial–mesenchymal transition, hypoxia and xenobiotic metabolism were altered. Collectively, our results suggest that CENP-E reduction triggers a gene expression program that recapitulates some features of tumor cells. Full article
(This article belongs to the Special Issue Molecular Insights into Centromere Assembly and Dysfunction)
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