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Mol Cell Biol, March 1998, p. 1257-1265, Vol. 18, No. 3
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
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Efficient Repair of Abasic Sites in DNA by
Mitochondrial Enzymes
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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