Unit:
Τομέας ΚλινικοεργαστηριακόςLibrary of the School of Health Sciences
Author:
Ntakou- Zamplara Katerina- Zoi
Dissertation committee:
Πατσούρης Ευστράτιος, Καθηγητής, Τμήμα Ιατρικής, ΕΚΠΑ
Κορκολοπούλου Πηνελόπη, Καθηγήτρια, Τμήμα Ιατρικής, ΕΚΠΑ
Θεοχάρης Σταμάτιος, Καθηγητής, Τμήμα Ιατρικής, ΕΚΠΑ
Πιπέρη Χριστίνα, Αν. Καθηγήτρια, Τμήμα Ιατρικής, ΕΚΠΑ
Φουστέρη Μαρία, Ερευνήτρια Β', ΕΚΕΒΕ Αλ. Φλέμινγκ
Χατζής Παντελεήμων, Ερευνητής Β', ΕΚΕΒΕ Αλ. Φλέμινγκ
Δήμα Αντιγόνη, Ερευνήτρια Γ', ΕΚΕΒΕ Αλ. Φλέμινγκ
Original Title:
Μελέτη του ρόλου των επιγενετικών μηχανισμών και των μηχανισμών μεταγωγής σήματος στη ρύθμιση της γονιδιακής έκφρασης: η λειτουργία των CS πρωτεϊνών
Translated title:
The role of epigenetics and signal transduction in the regulation of gene expression: the function of Cockayne Syndrome proteins
Summary:
In this study we focused on complex molecular responses that preserve gene
expression accuracy and genome integrity in the face of UV irradiation. We revealed a new
mechanism in response to UV , in which RNA polymerase II (RNAPII) molecules are dynamically
and synchronously released from promoter-proximal pausing sites (PPP) into elongation to
promote uniform and accelerated surveillance of the whole transcribed genome. The
maximised influx of de novo released RNAPII correlates with increased damage-sensing. In
turn, this transcription elongation ‘safe’ mode guarantees efficient DNA repair regardless of
damage location, gene size and transcription level. Accordingly, we detect low and
homogenous rates of mutational signatures associated with UV exposure or cigarette smoke
across all active genes. Our results were recently published (Lavigne et al., Nature
Communications 2017).
Moreover, aiming to shed light on the role of Cockayne Syndrome protein B (CSB)
protein in transcription reorganization after damage, we studied the response of cells with
defective CSB to UV irradiation. Using nascent RNA sequencing, we revealed a new wave of
transcription released from PPP as an early response to UV in contrast to previous studies.
This de novo wave is characterized by a slower rate in comparison to normal cells possibly due
to the blockage of RNAPII molecules at damaged sites. Whereas the initiation of transcription
seems unaffected, the elongating polymerases remain trapped in areas close to the 5’ prime
end of long genes, preventing the recovery of transcription. As a result, Cockayne Syndrome
cells lacking vital transcripts eventually activate apoptotic pathways. The results of the second
part of this study are included in a manuscript which is under submission for publication
(Ntakou-Zamplara et al.).
Main subject category:
Health Sciences
Keywords:
Cockayne Syndrome, Gene exression regulation, Transcription, Signal transduction, CSB, Genomic integrity
