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Genes 2018, 9(12), 615; https://doi.org/10.3390/genes9120615

Repetitive Fragile Sites: Centromere Satellite DNA as a Source of Genome Instability in Human Diseases

Laboratory of Chromosome and Cell Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
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Received: 5 November 2018 / Revised: 3 December 2018 / Accepted: 3 December 2018 / Published: 7 December 2018
(This article belongs to the Special Issue Chromosome Replication and Genome Integrity)
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Abstract

Maintenance of an intact genome is essential for cellular and organismal homeostasis. The centromere is a specialized chromosomal locus required for faithful genome inheritance at each round of cell division. Human centromeres are composed of large tandem arrays of repetitive alpha-satellite DNA, which are often sites of aberrant rearrangements that may lead to chromosome fusions and genetic abnormalities. While the centromere has an essential role in chromosome segregation during mitosis, the long and repetitive nature of the highly identical repeats has greatly hindered in-depth genetic studies, and complete annotation of all human centromeres is still lacking. Here, we review our current understanding of human centromere genetics and epigenetics as well as recent investigations into the role of centromere DNA in disease, with a special focus on cancer, aging, and human immunodeficiency–centromeric instability–facial anomalies (ICF) syndrome. We also highlight the causes and consequences of genomic instability at these large repetitive arrays and describe the possible sources of centromere fragility. The novel connection between alpha-satellite DNA instability and human pathological conditions emphasizes the importance of obtaining a truly complete human genome assembly and accelerating our understanding of centromere repeats’ role in physiology and beyond. View Full-Text
Keywords: centromere; alpha-satellite; genome stability; repetitive DNA; human genome; recombination; fragile sites; genome instability; replication; cancer; aging centromere; alpha-satellite; genome stability; repetitive DNA; human genome; recombination; fragile sites; genome instability; replication; cancer; aging
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Black, E.M.; Giunta, S. Repetitive Fragile Sites: Centromere Satellite DNA as a Source of Genome Instability in Human Diseases. Genes 2018, 9, 615.

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