The identification of a novel gene, MAPO2, that is involved in the induction of apoptosis triggered by O⁶-methylguanine.

O⁶-Methylguanine, one of alkylated DNA bases, is especially mutagenic. Cells containing this lesion are eliminated by induction of apoptosis, associated with the function of mismatch repair (MMR) proteins. A retrovirus-mediated gene-trap mutagenesis was used to isolate new genes related to the induc...

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Autores principales: Ryosuke Fujikane, Masayuki Sanada, Mutsuo Sekiguchi, Masumi Hidaka
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:32041a432ac944a8bde15029a19004932021-11-18T07:04:25ZThe identification of a novel gene, MAPO2, that is involved in the induction of apoptosis triggered by O⁶-methylguanine.1932-620310.1371/journal.pone.0044817https://doaj.org/article/32041a432ac944a8bde15029a19004932012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028632/?tool=EBIhttps://doaj.org/toc/1932-6203O⁶-Methylguanine, one of alkylated DNA bases, is especially mutagenic. Cells containing this lesion are eliminated by induction of apoptosis, associated with the function of mismatch repair (MMR) proteins. A retrovirus-mediated gene-trap mutagenesis was used to isolate new genes related to the induction of apoptosis, triggered by the treatment with an alkylating agent, N-methyl-N-nitrosourea (MNU). This report describes the identification of a novel gene, MAPO2 (O⁶-methylguanine-induced apoptosis 2), which is originally annotated as C1orf201. The MAPO2 gene is conserved among a wide variety of multicellular organisms and encodes a protein containing characteristic PxPxxY repeats. To elucidate the function of the gene product in the apoptosis pathway, a human cell line derived from HeLa MR cells, in which the MAPO2 gene was stably knocked down by expressing specific miRNA, was constructed. The knockdown cells grew at the same rate as HeLa MR, thus indicating that MAPO2 played no role in the cellular growth. After exposure to MNU, HeLa MR cells and the knockdown cells underwent cell cycle arrest at G₂/M phase, however, the production of the sub-G₁ population in the knockdown cells was significantly suppressed in comparison to that in HeLa MR cells. Moreover, the activation of BAK and caspase-3, and depolarization of mitochondrial membrane, hallmarks for the induction of apoptosis, were also suppressed in the knockdown cells. These results suggest that the MAPO2 gene product might positively contribute to the induction of apoptosis triggered by O⁶-methylguanine.Ryosuke FujikaneMasayuki SanadaMutsuo SekiguchiMasumi HidakaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e44817 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ryosuke Fujikane
Masayuki Sanada
Mutsuo Sekiguchi
Masumi Hidaka
The identification of a novel gene, MAPO2, that is involved in the induction of apoptosis triggered by O⁶-methylguanine.
description O⁶-Methylguanine, one of alkylated DNA bases, is especially mutagenic. Cells containing this lesion are eliminated by induction of apoptosis, associated with the function of mismatch repair (MMR) proteins. A retrovirus-mediated gene-trap mutagenesis was used to isolate new genes related to the induction of apoptosis, triggered by the treatment with an alkylating agent, N-methyl-N-nitrosourea (MNU). This report describes the identification of a novel gene, MAPO2 (O⁶-methylguanine-induced apoptosis 2), which is originally annotated as C1orf201. The MAPO2 gene is conserved among a wide variety of multicellular organisms and encodes a protein containing characteristic PxPxxY repeats. To elucidate the function of the gene product in the apoptosis pathway, a human cell line derived from HeLa MR cells, in which the MAPO2 gene was stably knocked down by expressing specific miRNA, was constructed. The knockdown cells grew at the same rate as HeLa MR, thus indicating that MAPO2 played no role in the cellular growth. After exposure to MNU, HeLa MR cells and the knockdown cells underwent cell cycle arrest at G₂/M phase, however, the production of the sub-G₁ population in the knockdown cells was significantly suppressed in comparison to that in HeLa MR cells. Moreover, the activation of BAK and caspase-3, and depolarization of mitochondrial membrane, hallmarks for the induction of apoptosis, were also suppressed in the knockdown cells. These results suggest that the MAPO2 gene product might positively contribute to the induction of apoptosis triggered by O⁶-methylguanine.
format article
author Ryosuke Fujikane
Masayuki Sanada
Mutsuo Sekiguchi
Masumi Hidaka
author_facet Ryosuke Fujikane
Masayuki Sanada
Mutsuo Sekiguchi
Masumi Hidaka
author_sort Ryosuke Fujikane
title The identification of a novel gene, MAPO2, that is involved in the induction of apoptosis triggered by O⁶-methylguanine.
title_short The identification of a novel gene, MAPO2, that is involved in the induction of apoptosis triggered by O⁶-methylguanine.
title_full The identification of a novel gene, MAPO2, that is involved in the induction of apoptosis triggered by O⁶-methylguanine.
title_fullStr The identification of a novel gene, MAPO2, that is involved in the induction of apoptosis triggered by O⁶-methylguanine.
title_full_unstemmed The identification of a novel gene, MAPO2, that is involved in the induction of apoptosis triggered by O⁶-methylguanine.
title_sort identification of a novel gene, mapo2, that is involved in the induction of apoptosis triggered by o⁶-methylguanine.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/32041a432ac944a8bde15029a1900493
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