Rad21 Haploinsufficiency Prevents ALT-Associated Phenotypes in Zebrafish Brain Tumors
Cohesin is a protein complex consisting of four core subunits responsible for sister chromatid cohesion in mitosis and meiosis, and for 3D genome organization and gene expression through the establishment of long distance interactions regulating transcriptional activity in the interphase. Both roles...
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| Format: | Article |
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MDPI AG
2020-11-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/11/12/1442 |
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| author | Aurora Irene Idilli Cecilia Pazzi Francesca dal Pozzolo Michela Roccuzzo Maria Caterina Mione |
| author_facet | Aurora Irene Idilli Cecilia Pazzi Francesca dal Pozzolo Michela Roccuzzo Maria Caterina Mione |
| author_sort | Aurora Irene Idilli |
| collection | DOAJ |
| description | Cohesin is a protein complex consisting of four core subunits responsible for sister chromatid cohesion in mitosis and meiosis, and for 3D genome organization and gene expression through the establishment of long distance interactions regulating transcriptional activity in the interphase. Both roles are important for telomere integrity, but the role of cohesin in telomere maintenance mechanisms in highly replicating cancer cells in vivo is poorly studied. Here we used a zebrafish model of brain tumor, which uses alternative lengthening of telomeres (ALT) as primary telomere maintenance mechanism to test whether haploinsufficiency for Rad21, a member of the cohesin ring, affects ALT development. We found that a reduction in Rad21 levels prevents ALT-associated phenotypes in zebrafish brain tumors and triggers an increase in <i>tert</i> expression. Despite the rescue of ALT phenotypes, tumor cells in rad21+/− fish exhibit an increase in DNA damage foci, probably due to a reduction in double-strand breaks repair efficiency. |
| first_indexed | 2024-03-10T14:26:30Z |
| format | Article |
| id | doaj.art-b85dfb98e6724175a45e0d1de4250089 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T14:26:30Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-b85dfb98e6724175a45e0d1de42500892023-11-20T22:57:17ZengMDPI AGGenes2073-44252020-11-011112144210.3390/genes11121442Rad21 Haploinsufficiency Prevents ALT-Associated Phenotypes in Zebrafish Brain TumorsAurora Irene Idilli0Cecilia Pazzi1Francesca dal Pozzolo2Michela Roccuzzo3Maria Caterina Mione4Experimental Cancer Biology, Department of Cellular, Computational and Integrative Biology-CIBIO, University of Trento, 38123 Trento, ItalyExperimental Cancer Biology, Department of Cellular, Computational and Integrative Biology-CIBIO, University of Trento, 38123 Trento, ItalyExperimental Cancer Biology, Department of Cellular, Computational and Integrative Biology-CIBIO, University of Trento, 38123 Trento, ItalyAdvanced Imaging Facility, Department of Cellular, Computational and Integrative Biology-CIBIO, University of Trento, 38123 Trento, ItalyExperimental Cancer Biology, Department of Cellular, Computational and Integrative Biology-CIBIO, University of Trento, 38123 Trento, ItalyCohesin is a protein complex consisting of four core subunits responsible for sister chromatid cohesion in mitosis and meiosis, and for 3D genome organization and gene expression through the establishment of long distance interactions regulating transcriptional activity in the interphase. Both roles are important for telomere integrity, but the role of cohesin in telomere maintenance mechanisms in highly replicating cancer cells in vivo is poorly studied. Here we used a zebrafish model of brain tumor, which uses alternative lengthening of telomeres (ALT) as primary telomere maintenance mechanism to test whether haploinsufficiency for Rad21, a member of the cohesin ring, affects ALT development. We found that a reduction in Rad21 levels prevents ALT-associated phenotypes in zebrafish brain tumors and triggers an increase in <i>tert</i> expression. Despite the rescue of ALT phenotypes, tumor cells in rad21+/− fish exhibit an increase in DNA damage foci, probably due to a reduction in double-strand breaks repair efficiency.https://www.mdpi.com/2073-4425/11/12/1442ALTcohesintelomereszebrafishbrain tumorsDNA damage |
| spellingShingle | Aurora Irene Idilli Cecilia Pazzi Francesca dal Pozzolo Michela Roccuzzo Maria Caterina Mione Rad21 Haploinsufficiency Prevents ALT-Associated Phenotypes in Zebrafish Brain Tumors Genes ALT cohesin telomeres zebrafish brain tumors DNA damage |
| title | Rad21 Haploinsufficiency Prevents ALT-Associated Phenotypes in Zebrafish Brain Tumors |
| title_full | Rad21 Haploinsufficiency Prevents ALT-Associated Phenotypes in Zebrafish Brain Tumors |
| title_fullStr | Rad21 Haploinsufficiency Prevents ALT-Associated Phenotypes in Zebrafish Brain Tumors |
| title_full_unstemmed | Rad21 Haploinsufficiency Prevents ALT-Associated Phenotypes in Zebrafish Brain Tumors |
| title_short | Rad21 Haploinsufficiency Prevents ALT-Associated Phenotypes in Zebrafish Brain Tumors |
| title_sort | rad21 haploinsufficiency prevents alt associated phenotypes in zebrafish brain tumors |
| topic | ALT cohesin telomeres zebrafish brain tumors DNA damage |
| url | https://www.mdpi.com/2073-4425/11/12/1442 |
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