Epigenetic & reparation
Publié le 18/11/2022
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Chromatin and DNA repair in yeast
Art: N.
Bouvier for G.
Almouzni
Chromatin and DNA repair in yeast
- INTRODUCTION:
DNA damaging agents/DNA repair pathways
DNA lesions in the context of chromatin
A yeast model to study response to DSB
Double Strand Break Detection and Signaling in S.
Cerevisiae
Double Strand Break repair in S.
Cerevisiae
- The histone code for DNA signaling and repair
- ATP-dependent nucleosome remodeling factors in DSB repair
- DNA lesions in the context of the Nucleus
- DSB intranuclear localisation in S.
cerevisiae
Art: N.
Bouvier for G.
Almouzni
DNA damaging agents and DNA repair pathways
from J.
H.
Hoeijmakers.
Nature (2001).
DNA lesions in the context of chromatin
1.
First evidence from UV irradiation
-photoproducts, persist in tracts of DNA which are rendered refractory to excision repair by
a 'mask' of protein (Wilkins and Hart, 1974)
The effect of chromatin structure on repair was first implicated by the observations of Wilkins and Hart (R.J.
Wilkins, R.W.
Hart, 1974) that
UV induced lesions in permeable human cell chromatin are less accessible to CPD cleavage enzymes in M.
luteus extracts than
permeable cells treated with high salt (to remove histones).
-UV induces chromatin relaxation (Smerdon et al., 1978)
Rubbi and Milner, 2003
Rubbi and Milner, 2003
DNA lesions in the context of chromatin
2.
The Access, Repair, Restore model
(Smerdon, 1991 and Green and Almouzni, 2002 )
(Groth et al., 2007)
A yeast model to study response to DSB
hml/rD strain
inducible
HO
hmrD
"
hmlD
Chr.
3
MATa
Tel
Cen
Tel
HML/R strain
"
inducible
HO
HML
Chr.
3
Tel
MATa
Cen
HMR
Tel
Double Strand Break Detection and Signaling in S.
Cerevisiae
- G2/M arrest
- DNA damage
inducible genes
- RNR regulation
Double Strand Break repair in S.
Cerevisiae
Homologous
Recombination
Non Homologous
End Joining
Van Attikum and Gasser(2005)
The histone code for DNA signaling and repair
Van Attikum and Gasser(2005)
The histone code for DNA signaling and repair
P
Mec1ATR/Tel1ATM
The last serine of C-term of H2A or variants is well conserved and rapidly phosphorylated around DSBs
(Downs et al.,2000)
IMR90 normal human fibroblasts
Unirradiated
(Shroff et al., 2004)
3 min after 0.6Gy
(Rocagou et al., 1999)
The histone code for DNA signaling and repair
P
Mec1ATR/Tel1ATM
An assembly platform rather than a recruitment signal for repair and signaling proteins:
-MRX complex
-Rad9
-Cohesins
-Histone modifiers (NuA4 histone acetyl transferase)
-Chromatin remodelers (INO80, SWR1)
53BP1 foci
(Celeste et al., 2003)
The histone code for DNA signaling and repair
H2O2 induced apoptosis
(Ahn et al., 2005)
P
Ste20MST1
Ub
repair (Driscoll et al., 2007)
replication (Han et al., 2007)
Hat1
HR (Qin....
»
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