Download How is coordinated DNA damage repair and control of mitotic

How is coordinated DNA damage repair and control of mitotic commitment ensuring longterm genomic stability during successive cell cycles?
Candidates are welcome for a Postdoctoral position at Gustave Roussy Cancer Campus,
Villejuif, France. Applications for funding will be submitted to European or French agencies
(EMBO fellowships…).
During proliferation, all somatic cells reproducibly execute an intermediate G2 phase, of up
to several hours, before mitotic commitment. This G2 phase is hypothesized to provide more
time for completion of the DNA replication program and/or repair of DNA damages
appearing during replication, before cell division. Entry into mitosis in mammals is tightly
regulated by the active state of a MEN (Mitotic Entry Network) signaling pathway, including
Aurora-A, Polo-like kinase 1 and CyclinB1-Cdk1 kinases (Gavet & Pines, 2010a, 2010b).
Surprisingly, how are coordinated DDR (DNA Damage Response) and MEN signaling
pathways in space and time during any cell cycle ensuring a timely entry into mitosis and
contributing to the maintenance of genomic stability remain poorly understood. Previous
investigations showed that conditional inactivation of Checkpoint protein 1 (Chk1) induce a
premature entry into mitosis during unperturbed cell cycles, suggesting that (some) DDR
pathways will control normal G2/M progression. Our main objective is to quantitatively
analyze spatio-temporal regulation of DDR signaling pathways during normal G2 phase and
to determine how it is coordinated with MEN activation and entry into mitosis. This project
will be strongly based on real time live cell imaging assays combined with the use of FRET
(Fluorescence Resonance Energy Transfer) biosensors of kinase activities (Gheghiani &
Gavet, 2014).
Our research group is located at the Gustave Roussy Institute, a leading Cancer Research
center in Europe (~ 20min from Paris city center) in the research unit UMR8200 CNRS
Genetic stability and oncogenesis. http://www.gustaveroussy.fr/fr/content/divisioncellulaire-et-stabilité-génomique. The Institute provide core facilities for live cell and
intravital imaging, flow cytometry, bioinformatics, viral vector production, genomics,
proteomics and animal housing. The fellow will join a stimulating environment with several
groups working on different aspects of DNA repair mechanisms and signaling pathways that
preserve genome integrity and prevent cancer.
Applications
Interested candidates are encouraged to send a CV and names of 2 referees to:
Olivier GAVET
GUSTAVE ROUSSY Cancer Campus
Cell division and genomic stability team
lab: +33 1 42 11 62 25
E-mail: [email protected]