PMID- 10467406
OWN - NLM
STAT- MEDLINE
DCOM- 19991004
LR  - 20211203
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 32
DP  - 1999 Aug 12
TI  - Suppression of the poly(ADP-ribose) polymerase activity by DNA-dependent protein 
      kinase in vitro.
PG  - 4616-25
AB  - It has been suggested that DNA-dependent protein kinase (DNA-PK) is a central
      component of DNA double-strand-break repair. The mechanism of DNA-PK action,
      however, has not been fully understood. Poly(ADP-ribose) polymerase (PARP) is
      another nuclear enzyme which has high affinity to DNA ends. In this study, we
      analysed the interaction between these two enzymes. First, DNA-PK was found to
      suppress the PARP activity and alters the pattern of poly(ADP-ribosyl)ation.
      Although DNA-PK phosphorylates PARP in a DNA-dependent manner, this modification 
      is unlikely to be responsible for the suppression of PARP activity, since this
      suppression occurs even in the absence of ATP. Conversely, PARP was found to
      ADP-ribosylate DNA-PK in vitro. However, the auto-phosphorylation activity of
      DNA-PK was not influenced by this modification. In a competitive electrophoretic 
      mobility shift assay, Ku 70/80 complex, the DNA binding component of DNA-PK, was 
      found to have higher affinity to a short fragment of DNA than does PARP.
      Furthermore, co-immunoprecipitation analysis suggested direct or close
      association between Ku and PARP. Thus, DNA-PK suppresses PARP activity, probably 
      through direct binding and/or sequestration of DNA-ends which serve as an
      important stimulator for both enzymes.
FAU - Ariumi, Y
AU  - Ariumi Y
AD  - Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
FAU - Masutani, M
AU  - Masutani M
FAU - Copeland, T D
AU  - Copeland TD
FAU - Mimori, T
AU  - Mimori T
FAU - Sugimura, T
AU  - Sugimura T
FAU - Shimotohno, K
AU  - Shimotohno K
FAU - Ueda, K
AU  - Ueda K
FAU - Hatanaka, M
AU  - Hatanaka M
FAU - Noda, M
AU  - Noda M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Antigens, Nuclear)
RN  - 0 (DNA, Viral)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 2.7.11.1 (DNA-Activated Protein Kinase)
RN  - EC 2.7.11.1 (PRKDC protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.6.4.- (DNA Helicases)
RN  - EC 3.6.4.12 (XRCC5 protein, human)
RN  - EC 3.6.4.12 (Xrcc6 protein, human)
RN  - EC 4.2.99.- (Ku Autoantigen)
SB  - IM
MH  - *Antigens, Nuclear
MH  - Cell Line, Transformed
MH  - *DNA Helicases
MH  - DNA, Viral/metabolism
MH  - DNA-Activated Protein Kinase
MH  - DNA-Binding Proteins/metabolism
MH  - Human T-lymphotropic virus 1/genetics
MH  - Humans
MH  - Ku Autoantigen
MH  - Nuclear Proteins/metabolism
MH  - Phosphorylation
MH  - *Poly(ADP-ribose) Polymerase Inhibitors
MH  - Poly(ADP-ribose) Polymerases/isolation & purification/metabolism
MH  - Protein Serine-Threonine Kinases/isolation & purification/*metabolism
EDAT- 1999/09/01 00:00
MHDA- 1999/09/01 00:01
CRDT- 1999/09/01 00:00
PHST- 1999/09/01 00:00 [pubmed]
PHST- 1999/09/01 00:01 [medline]
PHST- 1999/09/01 00:00 [entrez]
AID - 10.1038/sj.onc.1202823 [doi]
PST - ppublish
SO  - Oncogene. 1999 Aug 12;18(32):4616-25. doi: 10.1038/sj.onc.1202823.