A novel protein, MAPO1, that functions in apoptosis triggered by O6-methylguanine mispair in DNA

Oncogene
K KomoriMasumi Hidaka

Abstract

O(6)-Methylguanine produced in DNA induces mutation due to its ambiguous base-pairing properties during DNA replication. To suppress such an outcome, organisms possess a mechanism to eliminate cells carrying O(6)-methylguanine by inducing apoptosis that requires the function of mismatch repair proteins. To identify other factors involved in this apoptotic process, we performed retrovirus-mediated gene-trap mutagenesis and isolated a mutant that acquired resistance to a simple alkylating agent, N-methyl-N-nitrosourea (MNU). However, it was still sensitive to methyl methanesulfonate, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea, etoposide and ultraviolet irradiation. Moreover, the mutant exhibited an increased mutant frequency after exposure to MNU. The gene responsible was identified and designated Mapo1 (O(6)-methylguanine-induced apoptosis 1). When the expression of the gene was inhibited by small interfering RNA, MNU-induced apoptosis was significantly suppressed. In the Mapo1-defective mutant cells treated with MNU, the mitochondrial membrane depolarization and caspase-3 activation were severely suppressed, although phosphorylation of p53, CHK1 and histone H2AX was observed. The orthologs of the M...Continue Reading

References

Dec 15, 1977·Journal of Molecular Biology·C Coulondre, J H Miller
Oct 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·E L LoechlerJ M Essigmann
May 1, 1994·Mutation Research·T ItoM Sekiguchi
Mar 14, 1995·Proceedings of the National Academy of Sciences of the United States of America·G M Li, P Modrich
Sep 1, 1994·Experimental Cell Research·A CossarizzaC Franceschi
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A KatP Modrich
Mar 14, 1998·Carcinogenesis·W MeikrantzL Samson
Jun 6, 1998·Proceedings of the National Academy of Sciences of the United States of America·H KawateM Sekiguchi
Jul 25, 1998·Genes & Development·R Fishel
Sep 15, 1999·Proceedings of the National Academy of Sciences of the United States of America·M J Hickman, L D Samson
Apr 18, 2000·Mutation Research·A E Pegg
Aug 24, 2000·The Journal of Biological Chemistry·M Christmann, B Kaina
Oct 12, 2000·Molecular and Cellular Biology·L HaracskaL Prakash
Dec 26, 2001·Carcinogenesis·P Karran
Mar 14, 2002·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Geoffrey P Margison, Mauro F Santibáñez-Koref
Sep 19, 2003·DNA Repair·Yasumitsu TakagiMutsuo Sekiguchi
Apr 8, 2004·Molecular Cell·Mark J Hickman, Leona D Samson
Jun 25, 2008·Biochemical Pharmacology·Yasumitsu TakagiMutsuo Sekiguchi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis