An active alternative splicing isoform of human mitochondrial 8-oxoguanine DNA glycosylase (OGG1)

被引：17

作者：

Furihata C. ^{[1
,2
]}

机构：

[1] School of Science and Engineering, Aoyama Gakuin University, Sagamihara, Kanagawa

[2] Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, Setagayaku, Tokyo

来源：

Genes and Environment | / 37卷 / 1期

关键词：

Human 8-oxoguanine DNA glycosylase; Mitochondrial OGG1; OGG1; OGG1-1a; OGG1-1b; OGG1-2a;

D O I：

10.1186/s41021-015-0021-9

中图分类号：

学科分类号：

摘要：

Eight alternatively spliced isoforms of human 8-oxoguanine DNA glycosylase (OGG1) (OGG1-1a, -1b, -1c, -2a, -2b, -2c, -2d and -2e) are registered at the National Center for Biotechnology Information (NCBI). OGG1-1a is present in the nucleus, whereas the other seven isoforms are present in the mitochondria. Recombinant OGG1-1a has been purified and enzyme kinetics determined. OGG1(s) in mitochondria have not been fully characterized biochemically until recently. The major mitochondrial OGG1 isoform, OGG1-2a (also named β-OGG1), has also been expressed and purified; however, its activity is unresolved. Recently, we purified recombinant mitochondrial OGG1-1b and found that it was an active OGG1 enzyme. We reported its enzyme kinetics and compared the results with those of OGG1-1a. The reaction rate constant of OGG1-1b 8-oxoG glycosylase activity (kg) was 8-oxoG:C > > 8-oxoG:T > > 8-oxoG:G > 8-oxoG:A and was similar to that of OGG1-1a under single-turnover conditions ([E] > [S]). Both OGG1-1b and OGG1-1a showed high specificity towards 8-oxoG:C. The reaction rate constant of OGG1-1b N-glycosylase/DNA lyase activity (kgl) was 8-oxoG:C > 8-oxoG:T ∼ 8-oxoG:G > > 8-oxoG:A and that of OGG1-1a was 8-oxoG:C > 8-oxoG:T, 8-oxoG:G and 8-oxoG:A. The kgl of OGG1-1b and OGG1-1a is one order of magnitude lower than the corresponding kg value. OGG1-1b showed an especially low kgl towards 8-oxoG:A. Comparable expression of OGG1-1a and OGG1-1b was detected by RT-PCR in normal human lung tissue and lung cell lines. These results suggest that OGG1-1b is associated with 8-oxoG cleavage in human lung mitochondria and that the mechanism of this repair is similar to that of nuclear OGG1-1a. Currently, the other five mitochondrial OGG1 isoforms have not been isolated. I summarize information on OGG1 isoform mRNAs, coding DNA sequences and amino acid sequences that are archived by the National Center for Biotechnology Information. © 2015 Furihata.

引用

共 17 条

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