Pathology of DNA Replication

 

 

 

Genetic instability is a major feature of tumor cells and is associated with the process of carcinogenesis in humans. In many cases, such instability occurs during the S phase and is due to DNA replication defects. The enzymatic machinery of replication used to copy and reproduce the DNA is called “replisome”. Replisome progression is subject to numerous control systems because its disruption can produce changes in the genome. DNA replication may be hampered by barriers that slow, temporarily stop or block the progression of replicative DNA polymerases. These obstacles may have different causes: a) secondary structures in DNA, b) complex DNA-protein, c) changes in chromatin and d) DNA damage. If the arrested replication forks are not appropriately processed , chromosomal rearrangements (translocations, inversions or deletions) may occur and contribute to early stages of carcinogenesis. In this context, we study the functions of translesional DNA polymerases that may contribute to bypass break sites. Actually, we think that it is important to understand these aspects of DNA replication, both in terms of mechanisms of emergence of such obstacles and their functional consequences.

 

Group Leader : Jean-Charles Cadoret

Associate Professor,  university of Paris

+33 (0)157278087

jean-charles.cadoret(at)ijm.fr

@DNA_RepPath_lab

https://orcid.org/0000-0002-3827-5208

 

 

RESEARCHMEMBERSPUBLICATIONS

 

 

Research topics

 

Biologie quantitative et modélisation , Développement et évolution , Dynamique cellulaire et signalisation , Dynamique du génome et des chromosomes, Pathologies moléculaires et cellulaires

 

Selected publications

 

Fauchereau F, Shalev S, Chervinsky E, Fruchter RB, Legois B, Fellous M, Caburet S, Veitia RA.
A non-sense MCM9 mutation in a familial case of primary ovarian insufficiency.
Clin Genet
. 2016 Jan 14.
Abstract

Baldacci G, Hoffmann JS, Cadoret JC.
Impact of the DNA polymerase Theta on the DNA replication program.
Genom Data. 2014 Dec 5;3:90-3.
Abstract

Maric C, Bénard M.
Replication forks reverse at high frequency upon replication stress in Physarum polycephalum.
Chromosoma. 2014 Dec;123(6):577-85.
Abstract

Fernandez-Vidal A, Guitton-Sert L, Cadoret JC, Drac M, Schwob E, Baldacci G, Cazaux C, Hoffmann JS.
A role for DNA polymerase θ in the timing of DNA replication.
Nat Commun. 2014 Jul 3;5:4285.
Abstract

Delagoutte E, Heneman-Masurel A, Baldacci G.
Single-stranded DNA binding proteins unwind the newly synthesized double-stranded DNA of model miniforks.
Biochemistry 2011 50:932-944
Abstract

Delagoutte E,Baldacci G.
5’CAG and 5’CTG Repeats Create Differential Impediment to the Progression of a Minimal Reconstituted T4 Replisome Depending on the Concentration of dNTPs.
Mol Biol Int. 2011;2011:213824.
Abstract