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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/32041a432ac944a8bde15029a1900493
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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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The identification of a novel gene, MAPO2, that is involved in the induction of apoptosis triggered by O⁶-methylguanine.

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