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Identifier 000442169
Title XAB2 links pre-mRNA splicing with the DNA damage response during mammalian development
Alternative Title Η πρωτεΐνη XAB2 συνδέει το μάτισμα του RNA με την κυτταρική απάντηση στις βλάβες DNA κατά την διάρκεια της ανάπτυξης
Author Τσεκρέκου, Μαρία Π.
Thesis advisor Γαρίνης, Γεώργιος
Reviewer Αλεξανδράκη, Δέσποινα
Καλαντίδης, Κρίτων
Σπηλιανάκης, Χαράλαμπος
Τζαμαρίας, Δημήτρης
Δελιδάκης, Χρήστος
Ταλιανίδης, Ιωάννης
Abstract RNA splicing and the DNA damage response are intriguingly linked in mammals but the underlying mechanisms remain poorly understood. Using an in vivo biotinylation tagging approach in mice we show that XAB2, the human homologue of the yeast pre-mRNA-splicing factor SYF1 has a functional role in Nucleotide Excision Repair (NER) and the DNA damage response (DDR) in mammals. XAB2 interacts with the spliceosome factors PRP19, BCAS2 and Aquarius; it is part of the core spliceosome and binds to spliceosomal U4 and U6 snRNAs during hepatic development. Ablation of XAB2 leads to defective NER, intron retention, the aberrant accumulation of pre-mRNAs and to a faulty ATM/ATR DDR signaling. Using functional approaches, we find that XAB2 dissociates from RNA targets upon persistent DNA damage or transcription blockage and from spliceosomal RNAs in NER-defective developing livers. We propose that XAB2 functionally links NER and the spliceosomal response to DNA damage with important ramifications for the developmental defects associated with transcription-coupled DNA repair disorders.
Language English
Subject NER
Nucleotide excision repair
Επιδιόρθωση με εκτομή νουκλεοτιδίων
Issue date 2021-07-28
Collection   School/Department--School of Sciences and Engineering--Department of Biology--Doctoral theses
  Type of Work--Doctoral theses
Permanent Link https://elocus.lib.uoc.gr//dlib/2/b/b/metadata-dlib-1632218498-851201-16597.tkl Bookmark and Share
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