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Molecular and Cellular Biology, August 2003, p. 5919-5927, Vol. 23, No. 16
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.16.5919-5927.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Physical and Functional Interaction between DNA Ligase III{alpha} and Poly(ADP-Ribose) Polymerase 1 in DNA Single-Strand Break Repair

John B. Leppard, Zhiwan Dong, Zachary B. Mackey,{dagger} and Alan E. Tomkinson*

Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245

Received 28 April 2003/ Accepted 20 May 2003

The repair of DNA single-strand breaks in mammalian cells is mediated by poly(ADP-ribose) polymerase 1 (PARP-1), DNA ligase III{alpha}, and XRCC1. Since these proteins are not found in lower eukaryotes, this DNA repair pathway plays a unique role in maintaining genome stability in more complex organisms. XRCC1 not only forms a stable complex with DNA ligase III{alpha} but also interacts with several other DNA repair factors. Here we have used affinity chromatography to identify proteins that associate with DNA ligase III. PARP-1 binds directly to an N-terminal region of DNA ligase III immediately adjacent to its zinc finger. In further studies, we have shown that DNA ligase III also binds directly to poly(ADP-ribose) and preferentially associates with poly(ADP-ribosyl)ated PARP-1 in vitro and in vivo. Our biochemical studies have revealed that the zinc finger of DNA ligase III increases DNA joining in the presence of either poly(ADP-ribosyl)ated PARP-1 or poly(ADP-ribose). This provides a mechanism for the recruitment of the DNA ligase III{alpha}-XRCC1 complex to in vivo DNA single-strand breaks and suggests that the zinc finger of DNA ligase III enables this complex and associated repair factors to locate the strand break in the presence of the negatively charged poly(ADP-ribose) polymer.

* Corresponding author. Mailing address: Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, 15355 Lambda Dr., San Antonio, TX 78245. Phone: (210) 567-7327. Fax: (210) 567-7324. E-mail: TOMKINSON{at}UTHSCSA.EDU.

{dagger} Present address: Department of Pathology, University of California, San Francisco, San Francisco, CA 94143.

Molecular and Cellular Biology, August 2003, p. 5919-5927, Vol. 23, No. 16
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.16.5919-5927.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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