Title

N-methylpurines are heterogeneously repaired in human mitochondria but not evidently repaired in yeast mitochondria

Document Type

Article

Publication Date

1-2-2011

Abstract

Base excision repair (BER) of dimethyl sulfate induced N-methylpurines (NMPs) was measured at nucleotide resolution in the mitochondrial DNA (mtDNA) of cultured human and yeast (Saccharomyces cerevisiae) cells. NMPs were repaired with heterogeneous rates in the human mtDNA. The nearest-neighbor nucleotides significantly affected the repair rates: NMPs between pyrimidines were repaired much faster than those between purines, and those between a purine and a pyrimidine were repaired at intermediate rates. Repair intermediates of NMPs can also be detected at certain sites of the human mtDNA, indicating an ineffectiveness of processing the intermediates at these sites by the human mitochondrial BER machinery. In contrast to the human mtDNA, the yeast mtDNA did not show detectable repair of NMPs at any sites. Furthermore, a high level of spontaneous strand breaks exists exclusively at purine sites in the yeast mtDNA. Spontaneous NMPs or oxidative lesions were unlikely to be the major causes for the spontaneous strand breaks. Rather, spontaneous depurination combined with inefficient processing of DNA nicks or single-nucleotide gaps by the yeast mitochondrial BER machinery may result in the spontaneous strand breaks. Our results unveil a striking difference in BER between human and the yeast mitochondria.

Publication Source (Journal or Book title)

DNA repair

First Page

65

Last Page

72

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