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Home    A tale of two proteins : S. cerevisiae Rad9 DNA damage checkpoint protein and Aft1 transcription factor on the surveillance of DNA damage-prone chromatin under non DNA damage-induced conditions. Insights from genome-wide analyses.  

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Identifier 000388629
Title A tale of two proteins : S. cerevisiae Rad9 DNA damage checkpoint protein and Aft1 transcription factor on the surveillance of DNA damage-prone chromatin under non DNA damage-induced conditions. Insights from genome-wide analyses.
Alternative Title Μια ιστορία δύο πρωτεϊνών: Η πρωτεΐνη ελέγχου καταστροφής DNA ScRad9 και ο μεταγραφικός παράγοντας Aft1 στην επιτήρηση της ευαίσθητης σε καταστροφή DNA χρωματίνης υπό φυσιολογικές συνθήκες. Μελέτη με γονιδιωματικής κλίμακας αναλύσεις.
Author Ανδρεάδης, Χρήστος Κ.
Thesis advisor Αλεξανδράκη, Δέσποινα
Abstract DNA damage response and repair proteins are centrally involved in genome maintenance pathways. Yet, little is known about their functional role under non-DNA damage-inducing conditions. Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ~2% of the coding genome in the absence of exogenously-induced DNA damage. Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events.
Language English
Subject Chromatin immunoprecipitation
Genome integrity
Ακεραιότητα γονιδιώματος
Ανοσοκατακρήμνιση χρωματίνης
Issue date 2014-10-02
Collection   School/Department--School of Sciences and Engineering--Department of Biology--Doctoral theses
  Type of Work--Doctoral theses
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