Post-graduate theses
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Identifier |
000419780 |
Title |
Delineating the role of XAB2 in mammalian physiology |
Alternative Title |
Διελεύκανση του ρόλου της ΧΑΒ2 στη φυσιολογία των θηλαστικών |
Author
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Μπατσιώτος, Νικόλαος Π.
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Thesis advisor
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Γαρίνης, Γιώργος
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Reviewer
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Αλεξανδράκη, Δέσποινα
Ταλιανίδης, Γιάννης
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Abstract |
To maintain genome stability, which is continuously challenged by a variety of
environmental and endogenous agents, cells have evolved a battery of DNA damage
signaling and repair machineries. Nucleotide excision repair (NER), is a highly conserved
pathway which repairs a broad class of helix-distorting lesions. NER defects are
associated with cancer and premature aging, yet the neurological, developmental and
metabolic abnormalities observed in NER syndromes cannot be explained only by the
repair deficiency, which implies that NER factors function also beyond repair. Indeed, it
is currently known that NER factors are also involved in transcription, chromatin
remodelling and possibly pre-mRNA splicing. The possibility of a functional interplay
between DNA damage repair/response and pre-mRNA splicing has recently emerged.
Pre-mRNA splicing factors have been shown to either regulate, at the posttranscriptional
level, the proper expression of DNA Damage Response (DDR) genes or be
directly recruited at the site of damage. A protein linking pre-mRNA splicing with DNA
repair is XPA Binding protein 2 (XAB2), which has been involved in NER, transcription
and pre-mRNA splicing, its exact function, however, remains elusive. In order to
investigate the functional contribution of XAB2 in hepatic physiology, biotin-tagged
XAB2 mice were generated to allow the in vivo identification of the protein’s interactors.
Here, we show that XAB2 is a partner of the core spliceosome, through its interaction
with the PRP19 complex. Ablation of XAB2 results in defective splicing as shown by
extensive intron retention, suggesting that XAB2 is indispensable for proper pre-mRNA
processing. Moreover, we show that XAB2 binds pre-mRNAs and that this binding is lost
in the presence of DNA damage leading to accumulation of unspliced pre-mRNA.
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Language |
English |
Subject |
Alternative splicing |
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DNA damage |
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DNA βλάβες |
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Εναλλακτικό μάτισμα |
Issue date |
2018-11-23 |
Collection
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School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses
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Type of Work--Post-graduate theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/e/b/0/metadata-dlib-1543910526-640196-31180.tkl
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Views |
288 |