Satellite DNAs in Health and Disease

Ugarković, Đurđica; Sermek, Antonio; Ljubić, Sven; Feliciello, Isidoro

doi:10.3390/genes13071154

Cited by 15 publications

(23 citation statements)

References 137 publications

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“…Misregulation of satDNA expression can lead to various abnormalities in the genomic architecture, chromosome segregation and gametogenesis. Changes in copy number of satDNAs and their transcription rates may be associated with stress, environmental adaptations and pathological states, such as oncogenic transformation [ 18 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ].…”

Section: Functional Importance Of Satellite Dnas and Partnership With...mentioning

confidence: 99%

Satellite DNAs—From Localized to Highly Dispersed Genome Components

Šatović-Vukšić

Plohl

2023

Genes

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According to the established classical view, satellite DNAs are defined as abundant non-coding DNA sequences repeated in tandem that build long arrays located in heterochromatin. Advances in sequencing methodologies and development of specialized bioinformatics tools enabled defining a collection of all repetitive DNAs and satellite DNAs in a genome, the repeatome and the satellitome, respectively, as well as their reliable annotation on sequenced genomes. Supported by various non-model species included in recent studies, the patterns of satellite DNAs and satellitomes as a whole showed much more diversity and complexity than initially thought. Differences are not only in number and abundance of satellite DNAs but also in their distribution across the genome, array length, interspersion patterns, association with transposable elements, localization in heterochromatin and/or in euchromatin. In this review, we compare characteristic organizational features of satellite DNAs and satellitomes across different animal and plant species in order to summarize organizational forms and evolutionary processes that may lead to satellitomes’ diversity and revisit some basic notions regarding repetitive DNA landscapes in genomes.

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Section: Functional Importance Of Satellite Dnas and Partnership With...mentioning

confidence: 99%

Satellite DNAs—From Localized to Highly Dispersed Genome Components

Šatović-Vukšić

Plohl

2023

Genes

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“…Despite the initial ideas about transcriptionally silent pericentromeres, we know now that the DNA of all HSAT families (HSAT1-3) can be transcribed in a cell under certain circumstances (stress, malignization, cancer-associated polarization, differentiation, senescence, oogenesis, and embryogenesis) [ 19 , 25 , 41 , 42 , 43 ]. In cancer cells, HSAT DNA and RNA contribute to genetic instability [ 20 , 44 , 45 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…In tumors as a whole, pericentromeric transcripts transcribed in microenvironment cells (e.g., fibroblasts) can increase drug resistance, provoke inflammation, activate the innate immune system, etc. [ 19 , 26 , 27 , 41 ]. HSAT transcription is correlated with poor prognosis and lower survival [ 26 , 48 , 49 ] and is more prominent in advanced tumors [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Pericentromeric HSAT2 DNA Increases Expression of EMT Markers in Human Epithelial Cancer Cell Lines

Ponomartsev

Zilov

Gushcha

et al. 2023

IJMS

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Pericentromeric tandemly repeated DNA of human satellites 1, 2, and 3 (HS1, HS2, and HS3) is actively transcribed in some cells. However, the functionality of the transcription remains obscure. Studies in this area have been hampered by the absence of a gapless genome assembly. The aim of our study was to map a transcript that we have previously described as HS2/HS3 on chromosomes using a newly published gapless genome assembly T2T-CHM13, and create a plasmid overexpressing the transcript to assess the influence of HS2/HS3 transcription on cancer cells. We report here that the sequence of the transcript is tandemly repeated on nine chromosomes (1, 2, 7, 9, 10, 16, 17, 22, and Y). A detailed analysis of its genomic localization and annotation in the T2T-CHM13 assembly revealed that the sequence belonged to HSAT2 (HS2) but not to the HS3 family of tandemly repeated DNA. The transcript was found on both strands of HSAT2 arrays. The overexpression of the HSAT2 transcript increased the transcription of the genes encoding the proteins involved in the epithelial-to-mesenchymal transition, EMT (SNAI1, ZEB1, and SNAI2), and the genes that mark cancer-associated fibroblasts (VIM, COL1A1, COL11A1, and ACTA2) in cancer cell lines A549 and HeLa. Co-transfection of the overexpression plasmid and antisense nucleotides eliminated the transcription of EMT genes observed after HSAT2 overexpression. Antisense oligonucleotides also decreased transcription of the EMT genes induced by tumor growth factor beta 1 (TGFβ1). Thus, our study suggests HSAT2 lncRNA transcribed from the pericentromeric tandemly repeated DNA is involved in EMT regulation in cancer cells.

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“…A characteristic feature of hsrω is the presence of a long stretch of tandem satellite repeats at its 3-prime end (Johnson et al, 2011; McKechnie et al, 1998) which is reminiscent of sat III repeats seen at the 9q12 heterochromatic region (Jolly and Lakhotia, 2006). Microsatellites are among the most variable loci in the human genome and are prone to display copy number variations and aberrant transcription, often associated with disease conditions (Sonay et al, 2015; Ugarković et al, 2022). For instance, while on one hand the 9q12 locus is frequently deleted in bladder cancers (Hopman et al, 2002; Sauter et al, 1995), on the other increase in sat III levels is seen in cancer cell lines, such as in this study and others ((Chatterjee and Sengupta, 2022), for review see (Ugarković et al, 2022)).…”

Section: Discussionmentioning

confidence: 99%

A Gene Encoding an Architectural RNA,hsrω, is a Host Genetic Modifier of Cancer Progression inDrosophila

Bajpai

Kundu

et al. 2021

Preprint

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Cells incurring oncogenic hits are often eliminated by cell death via built-in anti-cancer defense mechanisms, broadly termed as intrinsic tumor suppression (ITS). Identification of genetic modifiers of ITS-induced cell death would provide better understanding of inherent tumor-resistance and/or susceptibility. Using a Drosophila model of loss of a tumor suppressor-mediated epithelial tumorigenesis, here we show that perturbations in levels of stress-responsive nuclear long non-coding RNA (lncRNA) hsrω gene, promote epithelial tumorigenesis. Thus, while somatic clones with loss of a tumor suppressor, Lgl, are eliminated by JNK-induced cell death, lgl mutant somatic clones induced either in an hsrω loss-of-function heterozygous genetic background, or upon cell autonomous up- or down-regulation of hsrω in lgl somatic clones, override the JNK-mediated cell death and progress to full blown tumors. These tumors display deregulation of Hippo pathway as seen from a gain of downstream target of inhibition, Diap1, an inhibitor of cell death. We finally show that downregulation in sat III non-coding RNA, a functional analog of hsrω in humans, increases sensitivity of cancer cells to cytotoxic stress-induced cell death. lncRNA hsrω, therefore, constitutes a novel genetic modifier of ITS in Drosophila and of stress-induced cell death in human cancers.SummaryA long non-coding RNA, hsrω, is a novel regulator of JNK-mediated intrinsic tumor suppression in Drosophila.Highlightslgl clones induced in hsrω heterozygous loss-of-function genetic background escape intrinsic tumor suppression (ITS).Perturbation of hsrω in lgl mutant clones, too, leads to their escape from ITS.hsrω homeostasis required for JNK-dependent ITS.Human sat III, a functional analog of hsrω, confers stress-resistant to human cancer cells.

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Satellite DNAs in Health and Disease

Cited by 15 publications

References 137 publications

Satellite DNAs—From Localized to Highly Dispersed Genome Components

Satellite DNAs—From Localized to Highly Dispersed Genome Components

Overexpression of Pericentromeric HSAT2 DNA Increases Expression of EMT Markers in Human Epithelial Cancer Cell Lines

A Gene Encoding an Architectural RNA,hsrω, is a Host Genetic Modifier of Cancer Progression inDrosophila

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