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Poly (ADP‐ribose) polymerase inhibits DNA replication by human replicative DNA polymerase α, δ and ε in vitro
Author(s) -
Eki Toshihiko
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)01280-6
Subject(s) - dna polymerase , proliferating cell nuclear antigen , dna polymerase delta , poly adp ribose polymerase , dna polymerase ii , dna replication , microbiology and biotechnology , dna clamp , processivity , primer (cosmetics) , polymerase , dna polymerase mu , biology , dna synthesis , eukaryotic dna replication , dna , dna repair , chemistry , biochemistry , circular bacterial chromosome , polymerase chain reaction , gene , reverse transcriptase , organic chemistry
The influence of poly (ADP‐ribose) polymerase (PARP) and poly ADP‐ribosylation on DNA synthesis supported by human replicative DNA polymerase (DNA pol) α, δ, and ε 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 δ, proliferating cell nuclear antigen (PCNA) and activator 1 (A1; RF‐C). Both DNA pol α and ε activities were decreased approximately 10‐fold under the poly ADP‐ribosylating condition. In contrast, DNA synthesis by DNA pol δ holoenzyme was not affected by poly ADP‐ribosylation like prokaryotic DNA pol's. The analysis of poly(dT) formed by DNA pol α and ε 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.