DNA Damage and Repair in the Immune System INSERM U768

SFRP 11/03/2008
Lésions de l’ADN
•Sensibilité individuelle
•Mécanismes de réparations
•Pathologies asociées
Intérêt du Système Immunitaire dans l’étude des
lésions de l’ADN et des mécanismes assurant leurs
réparations
« Stress » génotoxiques

SFRP 11/03/2008
Genetic plasticity in the immune system
V(D)J recombination
Cell proliferation
V(D)J recombination
Cell proliferation
CSR, SHM
Cell proliferation
Cell activation
Cell proliferation
Cell activation DNA “damages” / modifications
ÂProgrammed/natural
V(D)J recombination
CSR, SHM
ÂRandom/accidental/environmental
Cell proliferation
Stalling of replication forks
Telomere maintenance
Cell activation
Reactive oxygen species (ROS)

SFRP 11/03/2008
s
s
s
ss
s
s
s
SS
COOH
NH2
VαVβ
CαCβ
JαDβJβ
TCR α/β
Variable Domain
Variable Diversity
Joint Constant
VJC

SFRP 11/03/2008
V(D)J recombination
ÂDiversity of the immune system
ÂDevelopmental checkpoint of the adaptive immune system
Artemis
DNA-LigaseIV
Cernunnos

SFRP 11/03/2008
T-B-NK+ SCIDs
V(D)J recombination deficiency
ÂT-B-NK+ SCID
•20% of SCIDs
•Autosomal recessive inheritance
•HSC transplantation
ÂRag1/2 SCIDs
ÂRS-SCID
•T-B-NK+
•V(D)J recombination defect
•No Rag1/2 mutations
•Increased sensitivity to IR
•General DNA-dsb repair defect
V(D)J recombination
defect