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Mol Cell Biol, March 1998, p. 1257-1265, Vol. 18, No. 3
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Efficient Repair of Abasic Sites in DNA by Mitochondrial Enzymes

Kevin G. Pinz and Daniel F. Bogenhagen*

Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York 11794-8651

Received 21 August 1997/Returned for modification 22 September 1997/Accepted 3 December 1997

Mutations in mitochondrial DNA (mtDNA) cause a variety of relatively rare human diseases and may contribute to the pathogenesis of other, more common degenerative diseases. This stimulates interest in the capacity of mitochondria to repair damage to mtDNA. Several recent studies have shown that some types of damage to mtDNA may be repaired, particularly if the lesions can be processed through a base excision mechanism that employs an abasic site as a common intermediate. In this paper, we demonstrate that a combination of enzymes purified from Xenopus laevis mitochondria efficiently repairs abasic sites in DNA. This repair pathway employs a mitochondrial class II apurinic/apyrimidinic (AP) endonuclease to cleave the DNA backbone on the 5' side of an abasic site. A deoxyribophosphodiesterase acts to remove the 5' sugar-phosphate residue left by AP endonuclease. mtDNA polymerase gamma  fills the resulting 1-nucleotide gap. The remaining nick is sealed by an mtDNA ligase. We report the first extensive purification of mtDNA ligase as a 100-kDa enzyme that functions with an enzyme-adenylate intermediate and is capable of ligating oligo(dT) strands annealed to poly(rA). These properties together with preliminary immunological evidence suggest that mtDNA may be related to nuclear DNA ligase III.

* Corresponding author. Mailing address: Department of Pharmacological Sciences, State University of New York at Stony Brook, Basic Health Sciences T-8, Room 140, Stony Brook, NY 11794-8651. Phone: (516) 444-3068. Fax: (516) 444-3218. E-mail: dan{at}pharm.sunysb.edu.




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