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-H/F Phd in structural biology of DNA repair machineries

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Français - Anglais

Date Limite Candidature : mardi 26 octobre 2021

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General information

Reference : UMR9198-JEACHA-005
Workplace : ORSAY
Date of publication : Tuesday, October 5, 2021
Scientific Responsible name : Charbonnier
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 December 2021
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly

Description of the thesis topic

Structural study of gene rearrangement mechanisms in paramecium.
DNA double-strand breaks (DSBs) are genotoxic lesions that threaten the integrity of the genome. They can be caused
caused accidentally by exogenous or endogenous factors and are repaired either by homologous recombination (HR) or by non-homologous end joining (NHEJ). NHEJ involves direct ligation of the broken DNA ends, without the need for resection or sequence homology. Classical NHEJ is initiated by
binding of the ring-shaped Ku70/Ku80 (Ku) heterodimer to the DNA ends. Ku protects the ends from resection and, together with its partner DNA-PKcs, facilitates their synapsis to keep the two ends in close proximity. After the action of the DNA-processing enzymes, the Ligase 4-Xrcc4 complex catalyses the joining of the ends.
Although potentially dangerous, programmed DSBs (prDSBs) are essential for a number of physiological processes such as inter-homologous mixing of parental alleles during meiosis or the assembly of highly diverse immunoglobulin genes during lymphocyte differentiation. In these cases, any defect in DNA cleavage or subsequent repair of DSBs can cause chromosomal aberrations leading to serious pathologies (e.g. aneuploidies
and infertility, or translocation-induced immunodeficiencies and lymphomas). Our working hypothesis is that programmed genome rearrangements involving prDSBs require the establishment of a tight coupling between DNA cleavage and DSB repair to avoid endangering genome stability.

Work Context

We use paramecium as a model organism to study the coupling between DNA cleavage and repair during programmed double-strand breaks. Our laboratory is located at CEA Saclay within the I2BC and is due to join the CNRS campus in Gif-s-Yvette in 2022. We are working on the structural study of DNA repair mechanisms using X-ray crystallography and CryoEM

Constraints and risks

No particular risk or constraints

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