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Media type:
E-Article
Title:
Enzyme Kinetics of an Alternative Splicing Isoform of Mitochondrial 8‐Oxoguanine DNA Glycosylase, OGG1‐1b, and Compared with the Nuclear OGG1‐1a
Description:
<jats:title>ABSTRACT</jats:title><jats:p>Eight alternatively spliced isoforms of human 8‐oxoguanine DNA glycosylase (<jats:italic>OGG1</jats:italic>) (<jats:italic>OGG1‐</jats:italic>1a to ‐1c and ‐2a to ‐2e) are registered in the National Center for Biotechnology Information. OGG1(s) in mitochondria have not yet been fully characterized biochemically. In this study, we purified mitochondrial recombinant OGG1‐1b protein and compared its activity with nuclear OGG1‐1a protein. The reaction rate constant (<jats:italic>k<jats:sub>g</jats:sub></jats:italic>) of the 7,8‐dihydro‐8‐oxoguanine (8‐oxoG) glycosylase activity of OGG1‐1b was 8‐oxoG:C >> 8‐oxoG:T >> 8‐oxoG:G > 8‐oxoG:A (7.96, 0.805, 0.070, and 0.015 min<jats:sup>−1</jats:sup>, respectively) and that of the <jats:italic>N</jats:italic>‐glycosylase/DNA lyase activity (<jats:italic>k<jats:sub>gl</jats:sub></jats:italic>) of OGG1‐1b was 8‐oxoG:C > 8‐oxoG:T ≃8‐oxoG:G >> 8‐oxoG:A (0.286, 0.079, 0.040, and negligible min<jats:sup>−1</jats:sup>, respectively). These reaction rate constants were similar to those of OGG1‐1a except for <jats:italic>k<jats:sub>gl</jats:sub></jats:italic> against 8‐oxoG:A. APEX nuclease 1 was required to promote DNA strand breakage by OGG1‐1b. These results suggest that OGG1‐1b is associated with 8‐oxoG cleavage in human mitochondria and that the mechanism of this repair is similar to that of nuclear OGG1‐1a.</jats:p>