PUBLICATION
Rad21 Haploinsufficiency Prevents ALT-Associated Phenotypes in Zebrafish Brain Tumors
- Authors
- Idilli, A.I., Pazzi, C., Dal Pozzolo, F., Roccuzzo, M., Mione, M.C.
- ID
- ZDB-PUB-201208-4
- Date
- 2020
- Source
- Genes 11(12): (Journal)
- Registered Authors
- Idilli, Aurora
- Keywords
- ALT, DNA damage, brain tumors, cohesin, telomeres, zebrafish
- MeSH Terms
-
- Animals
- Brain Neoplasms/genetics*
- Cell Cycle Proteins/genetics
- Cell Line, Tumor
- Chromosomal Proteins, Non-Histone/genetics
- DNA Breaks, Double-Stranded
- DNA Repair/genetics
- DNA-Binding Proteins/genetics*
- Haploinsufficiency/genetics*
- HeLa Cells
- Humans
- Phenotype
- Telomere/genetics*
- Zebrafish/genetics*
- PubMed
- 33266037 Full text @ Genes (Basel)
Citation
Idilli, A.I., Pazzi, C., Dal Pozzolo, F., Roccuzzo, M., Mione, M.C. (2020) Rad21 Haploinsufficiency Prevents ALT-Associated Phenotypes in Zebrafish Brain Tumors. Genes. 11(12):.
Abstract
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 tert 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping