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| Identifier |
000404465 |
| Title |
The functional role of XAB2 in Embryonic Stem Cells |
| Alternative Title |
Ο λειτουργικός ρόλος της XAB2 στα εμβρυϊκά βλαστικά κύτταρα |
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Author
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Λεδάκη, Ελευθερία
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Thesis advisor
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Γαρίνης, Γ.
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Reviewer
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Σπηλιανάκης, Χ.
Καμπράνης, Σ.
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| Abstract |
Nucleotide Excision Repair is an evolutionary conserved DNA repair pathway which safeguards the genome and ensures its faithful transmission to progeny. However, several proteins participating in NER have distinct roles further to DNA repair which could provide a direct link of NER defects to development and disease. Such a protein is XAB2 involved in transcription, two DNA repair pathways, TC-NER and HR and pre-mRNA splicing. XAB2 gene disruption leads to pre-implantation lethality but its function is yet to be elucidated. We therefore used siRNA assays to study its role and efficiently knocked-down XAB2 in JM8A3.N1, bio XAB2;birA mESCs and MEFs both in RNA and protein levels. Assessing the impact of XAB2 elimination in transcription, showed reduction of RNA-DNA hybrids in the nucleoli of JM8A3.N1 mESCs and MEFs coupled with decrease in RNApolII protein levels. Both phenotypes where rescued when overexpressing XAB2 in MEFs. Experiments conducted to validate its participation in NER found XAB2 not interacting with previously presented factors like RNA polII and XPA and its knock-down not causing damage studied by γH2Ax staining. RNA-seq data from siRNA XAB2 samples presented down-regulated genes targeted to the ribosomal group. These results suggest a probable role of XAB2 in transcription and splicing of ribosomal genes.
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| Language |
English |
| Subject |
Pre-mRNA splicing |
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Ribosome |
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Μονοπάτι επιδιόρθωσης DNA μέσω εκτομής νουκλεοτιδίων |
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Ριβόσωμα |
| Issue date |
2016-12-13 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Post-graduate theses
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Type of Work--Post-graduate theses
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| Views |
281 |
The functional role of XAB2 in Embryonic Stem Cells
