DNA polymerase beta -mediated long patch base excision repair. Poly(ADP-ribose)polymerase-1 stimulates strand displacement DNA synthesis

Recently, photoaffinity labeling experiments with mouse cell extracts suggested that PARP-1 functions as a surveillance protein for a stalled BER intermediate. To further understand the role of PARP-1 in BER, we examined the DNA synthesis and flap excision steps in long patch BER using a reconstitut...

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Published inThe Journal of biological chemistry Vol. 276; no. 35; pp. 32411 - 32414
Main Authors Prasad, R, Lavrik, O I, Kim, S J, Kedar, P, Yang, X P, Vande Berg, B J, Wilson, S H
Format Journal Article
LanguageEnglish
Published United States 31.08.2001
Subjects
Amino Acid Substitution
Base Sequence
Circular Dichroism
DNA - biosynthesis
DNA - chemistry
DNA - metabolism
DNA Glycosylases
DNA Polymerase beta - chemistry
DNA Polymerase beta - metabolism
DNA Repair
DNA Replication
Endodeoxyribonucleases - metabolism
Flap Endonucleases
Humans
Mutagenesis, Site-Directed
N-Glycosyl Hydrolases - metabolism
Oligodeoxyribonucleotides - chemistry
Oligodeoxyribonucleotides - metabolism
PARP-1 protein
pol ^b protein
Poly(ADP-ribose) Polymerases - metabolism
Protein Conformation
Recombinant Proteins - chemistry
Recombinant Proteins - metabolism
Uracil-DNA Glycosidase
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Summary:Recently, photoaffinity labeling experiments with mouse cell extracts suggested that PARP-1 functions as a surveillance protein for a stalled BER intermediate. To further understand the role of PARP-1 in BER, we examined the DNA synthesis and flap excision steps in long patch BER using a reconstituted system containing a 34-base pair BER substrate and five purified human enzymes: uracil-DNA glycosylase, apurinic/apyrimidinic endonuclease, DNA polymerase beta, flap endonuclease-1 (FEN-1), and PARP-1. PARP-1 stimulates strand displacement DNA synthesis by DNA polymerase beta in this system; this stimulation is dependent on the presence of FEN-1. PARP-1 and FEN-1, therefore, cooperate to activate long patch BER. The results are discussed in the context of a model for BER sub-pathway choice, illustrating a dual role for PARP-1 as a surveillance protein for a stalled BER intermediate and an activating factor for long patch BER DNA synthesis.
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ISSN:0021-9258
DOI:10.1074/jbc.C100292200