Poly (ADP-ribose) polymerase inhibits DNA replication by human replicative DNA polymerase alpha, delta and epsilon in vitro.
FEBS Lett
; 356(2-3): 261-6, 1994 Dec 19.
Article
in En
| MEDLINE
| ID: mdl-7805850
ABSTRACT
The influence of poly (ADP-ribose) polymerase (PARP) and poly ADP-ribosylation on DNA synthesis supported by human replicative DNA polymerase (DNA pol) alpha, delta, and epsilon has been examined using the replication system containing poly(dA)4500-oligo(dT)12-18 as the template primer. PARP alone inhibited the pol activities in a dose-dependent manner even in the presence of the accessory factors for DNA pol delta, proliferating cell nuclear antigen (PCNA) and activator 1 (Al; RF-C). Both DNA pol alpha and epsilon activities were decreased approximately 10-fold under the poly ADP-ribosylating condition. In contrast, DNA synthesis by DNA pol delta holoenzyme was not affected by poly ADP-ribosylation like prokaryotic DNA pol's. The analysis of poly(dT) formed by DNA pol alpha and epsilon indicated that poly ADP-ribosylation mainly reduced the frequency of replication. These observations suggest a possibility that PARP acts as a negative regulator for the initiation of DNA replication upon cellular DNA damage.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Poly(ADP-ribose) Polymerases
/
DNA Polymerase II
/
DNA-Directed DNA Polymerase
/
DNA Replication
Limits:
Humans
Language:
En
Journal:
FEBS Lett
Year:
1994
Type:
Article
Affiliation country:
Japan