The Shizosaccharomyces pombe homolog (SpMYH) of the Escherichia coli MutY is required for removal of guanine from 8-oxoguanine/guanine mispairs to prevent G: C to C:G transversions

Takashi Doi, Shinichirou Yonekura, Keizo Tano, Shinji Yasuhira, Shuji Yonei, Qiu Mei Zhang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The frequency of G:C→C:G transversions significantly increases upon exposure of cells to ionizing radiation or reactive oxygen species. Transversions can be prevented by base excision repair, which removes the causative modified bases from DNA. Our previous studies revealed that MutY is responsible for removing guanine from 7,8-dihydro-8-oxoguanine/guanine mispairs (8-oxoG/G) and prevents the generation of G:C→C:G transversions in E. coli. SpMYH, a homolog of E. coli MutY, had been identified and characterized in the fission yeast S. pombe. Purified SpMYH has adenine DNA glycosylase activity on A/8-oxoG and A/G mismatch-containing oligonucleotides. In this study, we examined whether SpMYH has a similar activity allowing it to remove G from 8-oxoG/G in DNA. The purified SpMYH tightly bound to duplex oligonucleotides containing 8-oxoG/G and removed the unmodified G from 8-oxoG/G as efficiently as A from 8-oxoG/A. The activity was absent in the cell extract prepared from an SpMYH-knockout strain of S. pombe. The expression of SpMYH markedly reduced the frequency of spontaneous G:C→ C:G transversions in the E. coli mutY mutant. These results demonstrate that SpMYH is involved in the repair of 8-oxoG/G, by which it prevents mutations induced by oxidative stress in S. pombe.

Original languageEnglish
Pages (from-to)205-214
Number of pages10
JournalJournal of Radiation Research
Volume46
Issue number2
DOIs
Publication statusPublished - Jun 2005
Externally publishedYes

Fingerprint

guanines
guanine
Guanine
Escherichia
Schizosaccharomyces
Escherichia coli
deoxyribonucleic acid
oligonucleotides
Oligonucleotides
DNA
DNA Glycosylases
glycosylases
Schizosaccharomyces pombe
yeast
adenines
adenine
mutations
DNA repair
Ionizing Radiation
ionizing radiation

Keywords

  • 8-Oxoguanine
  • Base Excision repair
  • Base substitution
  • MutY/S
  • S. pombe

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Radiation

Cite this

The Shizosaccharomyces pombe homolog (SpMYH) of the Escherichia coli MutY is required for removal of guanine from 8-oxoguanine/guanine mispairs to prevent G : C to C:G transversions. / Doi, Takashi; Yonekura, Shinichirou; Tano, Keizo; Yasuhira, Shinji; Yonei, Shuji; Zhang, Qiu Mei.

In: Journal of Radiation Research, Vol. 46, No. 2, 06.2005, p. 205-214.

Research output: Contribution to journalArticle

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abstract = "The frequency of G:C→C:G transversions significantly increases upon exposure of cells to ionizing radiation or reactive oxygen species. Transversions can be prevented by base excision repair, which removes the causative modified bases from DNA. Our previous studies revealed that MutY is responsible for removing guanine from 7,8-dihydro-8-oxoguanine/guanine mispairs (8-oxoG/G) and prevents the generation of G:C→C:G transversions in E. coli. SpMYH, a homolog of E. coli MutY, had been identified and characterized in the fission yeast S. pombe. Purified SpMYH has adenine DNA glycosylase activity on A/8-oxoG and A/G mismatch-containing oligonucleotides. In this study, we examined whether SpMYH has a similar activity allowing it to remove G from 8-oxoG/G in DNA. The purified SpMYH tightly bound to duplex oligonucleotides containing 8-oxoG/G and removed the unmodified G from 8-oxoG/G as efficiently as A from 8-oxoG/A. The activity was absent in the cell extract prepared from an SpMYH-knockout strain of S. pombe. The expression of SpMYH markedly reduced the frequency of spontaneous G:C→ C:G transversions in the E. coli mutY mutant. These results demonstrate that SpMYH is involved in the repair of 8-oxoG/G, by which it prevents mutations induced by oxidative stress in S. pombe.",
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