Mutation Spectrum Induced by 8-Bromoguanine, a Base Damaged by Reactive Brominating Species, in Human Cells
| Autor: | Satoki Nakamura, Hisami Kato, Masanori Goto, Haruki Yoshida, Emi Tsuzaki, Yusuke Inoue, Haruhiko Sugimura, Kazuya Shinmura, Hong Tao |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Aging Guanine Article Subject NEIL1 Biology Transfection Biochemistry 03 medical and health sciences chemistry.chemical_compound Plasmid Shuttle vector MUTYH Cell Line Tumor Humans lcsh:QH573-671 lcsh:Cytology Cell Biology General Medicine Molecular biology Thymine 030104 developmental biology chemistry DNA glycosylase Mutation DNA Research Article |
| Zdroj: | Oxidative Medicine and Cellular Longevity Oxidative Medicine and Cellular Longevity, Vol 2017 (2017) |
| ISSN: | 1942-0994 1942-0900 |
| DOI: | 10.1155/2017/7308501 |
| Popis: | To date, the types of mutations caused by 8-bromoguanine (8BrG), a major base lesion induced by reactive brominating species during inflammation, in human cells and the 8BrG repair system remain largely unknown. In this study, we performed asupFforward mutation assay using a shuttle vector plasmid containing a single 8BrG in three kinds of human cell lines and revealed that 8BrG in DNA predominantly induces a G → T mutation but can also induce G → C, G → A, and delG mutations in human cells. Next, we tested whether eight kinds of DNA glycosylases (MUTYH, MPG, NEIL1, OGG1, SMUG1, TDG, UNG2, and NTHL1) are capable of repairing 8BrG mispairs with any of the four bases using a DNA cleavage activity assay. We found that both the SMUG1 protein and the TDG protein exhibit DNA glycosylase activity against thymine mispaired with 8BrG and that the MUTYH protein exhibits DNA glycosylase activity against adenine mispaired with 8BrG. These results suggest that 8BrG induces some types of mutations, chiefly a G → T mutation, in human cells, and some DNA glycosylases are involved in the repair of 8BrG. |
| Databáze: | OpenAIRE |
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