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Originally published In Press as doi:10.1074/jbc.C100292200 on July 5, 2001

J. Biol. Chem., Vol. 276, Issue 35, 32411-32414, August 31, 2001
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ACCELERATED PUBLICATION
DNA Polymerase beta -mediated Long Patch Base Excision Repair
POLY(ADP-RIBOSE) POLYMERASE-1 STIMULATES STRAND DISPLACEMENT DNA SYNTHESIS*

Rajendra PrasadDagger , Olga I. LavrikDagger , Soon-Jong KimDagger , Padmini KedarDagger , Xiao-Ping YangDagger , Brian J. Vande BergDagger , and Samuel H. WilsonDagger ||

From the Dagger  Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709

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.

* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

|| To whom correspondence should be addressed: Laboratory of Structural Biology, NIEHS, National Institutes of Health, 111 T.W. Alexander Dr., Research Triangle Park, NC 27709. Tel.: 919-541-3267; Fax: 919-541-3592; E-mail: wilson5@niehs.nih.gov.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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