Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.4.2.30 (
PARP
)
13,611
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Inhibition of
PARP
activity results in extreme sensitization to MMS-induced cell killing in cultured mouse fibroblasts. In these MMS-treated cells,
PARP
inhibition is accompanied by an accumulation of S-phase cells that requires signaling by the checkpoint kinase ATR [J.K.
Horton
, D.F. Stefanick, J.M. Naron, P.S. Kedar, S.H. Wilson, Poly(ADP-ribose) polymerase activity prevents signaling pathways for cell cycle arrest following DNA methylating agent exposure, J. Biol. Chem. 280 (2005) 15773-15785]. Here, we examined mouse fibroblast extracts for formation of a complex that may reflect association between the damage responsive proteins
PARP-1
and ATR. Co-immunoprecipitation of
PARP-1
and ATR was observed in extracts prepared from MMS-treated cells, but not under conditions of
PARP
inhibition. Further, our experiments demonstrated PAR-adduction of ATR in extracts from control and MMS-treated cells. An interaction between purified ATR and
PARP-1
was similarly demonstrated, suggesting that the observed co-immunoprecipitation of ATR and
PARP-1
from cell extracts may be due to a direct interaction between the two enzymes. In addition, purified recombinant ATR is a substrate for poly(ADP-ribosyl)ation by
PARP-1
, and poly(ADP-ribose) adduction of
PARP-1
and ATR resulted in an increase in
PARP-1
and ATR co-immunoprecipitation.
...
PMID:Interaction between PARP-1 and ATR in mouse fibroblasts is blocked by PARP inhibition. 1869 76
