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Interplay between RNA Pol II transcription and DNA replication

Project Description

RNA Pol II transcription and DNA replication are the two essential processes that use as a substrate the DNA in our cells, allowing them to express the content of their genetic information and to propagate these instructions to daughter cells. However, the DNA can be engaged only by one of these processes at any given time and we know that transcription can impair DNA replication inducing DNA damage and genome instability. In contexts of defective transcription this instability is furthermore greatly increased. Importantly, transcription-induced genome instability has also a direct impact on human health as associated cancer development and neurological disorders.
Aims of the project and methods:
For all these reasons, we are interested in investigating the full relationship between RNA Pol II transcription and DNA replication using a systemic approach.
i) Genome-wide next generation sequencing analyses of both transcription and DNA replication;
ii) Cell biology studies to characterise the impact of the interference between transcription and replication on genome stability (immune-fluorescence staining of DNA damage sites, activation of the DNA damage response by immunoblotting);
iii) Functional studies to characterise the roles of factors involved in coordinating, and resolving conflicting situations, between these two processes (impact of the RNAi of specific factors on genome-wide coordination between transcription and replication and on the DNA damage levels).
All in all, we are defining how the impairment of one of these two processes affects directly the other.

Funding Notes

Full eligibility criteria:
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Saponaro et al., RECQL5 controls transcript elongation and suppresses genome instability associated with transcription stress. Cell 2014; doi: 10.1016/j.cell.2014.03.048
Williamson et al., UV irradiation induces a non-coding RNA that functionally opposes the protein encoded by the same gene. Cell 2017; doi:10.1016/j.cell.2017.01.019
Bowry et al., BET inhibition induces HEXIM1- and RAD51-dependent conflicts between transcription and replication. Cell Reports in press
Higgs et al., Histone Methylation by SETD1A Protects Nascent DNA through the Nucleosome Chaperone Activity of FANCD2. Mol Cell 2018; doi: 10.1016/j.molcel.2018.05.018.

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