DRF: Thesis SL-DRF-20-0379

RESEARCH FIELD
Bioinformatics, bio-molecular simulation / Life Sciences

TITLE
Computational integration and modelling of DNA repair kinetics in eukaryotes

ABSTRACT
Maintenance of genome integrity is essential for the normal cell function. Different mechanisms have evolved to repair DNA damages
induced by genotoxic agents or cellular metabolism. In human, DNA repair dysfunctions lead to severe diseases including cancer,
neurological and premature-aging disorders. DNA repair is coupled with transcription to ensure the efficient removal of DNA lesions on
actively transcribed genes. Despite intensive studies, it remains poorly understood how DNA repair machinery is assembled, orchestrates
its actions and couples with transcription in vivo, notably on the genomic scale. Recently, we discovered a novel link between nucleotide
excision repair pathway and the Mediator complex, a crucial coregulator of transcription conserved in all eukaryotes. In this project, we will
develop computational tools for integrative analysis of DNA repair kinetics after UV irradiation in both budding yeast and human cells,
using many functional genomics data produced by the laboratory. Analysis of such intricate process at the genomic scale requires the
integration of heterogeneous and complex data including DNA damage distribution, DNA repair protein binding, transcription activity and
chromatin state. Moreover, we will model the assembly kinetics of DNA repair machinery, as well as the repair kinetics of DNA damages
and the transcription restart when repair is completed. We expect that this work will provide particularly innovative concepts for DNA repair
mechanisms on a genomic scale and help us to reach a deeper understanding of recruitment mechanisms for DNA repair proteins and the
Mediator function connecting transcription and DNA repair. The project will reinforce CEA expertise in the NGS data analysis and
modelling. It should form a fundamental biology basis, supporting innovative research in radiobiology and contributing to technologies for
the future medicine. Expected results will open new horizons for investigating the genome-wide DNA repair phenomena associated with
transcription and will shed a new light on fundamental and disease-relevant processes of life.

LOCATION
Institut des sciences du vivant Frédéric JOLIOT
Service de Biologie Intégrative et Génétique Moléculaire
Laboratoire de Transcription et Génomique
Place: Saclay
Start date of the thesis: 01/10/2020

CONTACT PERSON
Cyril DENBY WILKES
CEA
DRF/JOLIOT//SBIGEM
CEA/Saclay
SBIGeM, bât. 144
91191 Gif-sur-Yvette cedex
France

Commissariat à l'énergie atomique et aux énergies alternatives 1
Institut national des sciences et techniques nucléaires
www­instn.cea.fr
 Phone number: +33 1 69 08 51 43
Email: cyril.denby-wilkes@cea.fr

UNIVERSITY / GRADUATE SCHOOL

Paris-Saclay
Structure et Dynamique des Systèmes Vivants

FIND OUT MORE

https://www.i2bc.paris-saclay.fr/spip.php?article395

THESIS SUPERVISOR
Julie SOUTOURINA
CEA
DRF/JOLIOT/SBIGeM/LTG
CEA/Saclay
SBIGeM
Bât. 144
91191 Gif-sur-Yvette Cedex France

Commissariat à l'énergie atomique et aux énergies alternatives 2
Institut national des sciences et techniques nucléaires
www­instn.cea.fr

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