| http://purl.uniprot.org/citations/32144205 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32144205 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32144205 | http://www.w3.org/2000/01/rdf-schema#comment | "MutT homologue 1 (MTH1) removes oxidized nucleotides from the nucleotide pool and thereby prevents their incorporation into the genome and thereby reduces genotoxicity. We previously reported that MTH1 is an efficient catalyst of O6-methyl-dGTP hydrolysis suggesting that MTH1 may also sanitize the nucleotide pool from other methylated nucleotides. We here show that MTH1 efficiently catalyzes the hydrolysis of N6-methyl-dATP to N6-methyl-dAMP and further report that N6-methylation of dATP drastically increases the MTH1 activity. We also observed MTH1 activity with N6-methyl-ATP, albeit at a lower level. We show that N6-methyl-dATP is incorporated into DNA in vivo, as indicated by increased N6-methyl-dA DNA levels in embryos developed from MTH1 knock-out zebrafish eggs microinjected with N6-methyl-dATP compared with noninjected embryos. N6-methyl-dATP activity is present in MTH1 homologues from distantly related vertebrates, suggesting evolutionary conservation and indicating that this activity is important. Of note, N6-methyl-dATP activity is unique to MTH1 among related NUDIX hydrolases. Moreover, we present the structure of N6-methyl-dAMP-bound human MTH1, revealing that the N6-methyl group is accommodated within a hydrophobic active-site subpocket explaining why N6-methyl-dATP is a good MTH1 substrate. N6-methylation of DNA and RNA has been reported to have epigenetic roles and to affect mRNA metabolism. We propose that MTH1 acts in concert with adenosine deaminase-like protein isoform 1 (ADAL1) to prevent incorporation of N6-methyl-(d)ATP into DNA and RNA. This would hinder potential dysregulation of epigenetic control and RNA metabolism via conversion of N6-methyl-(d)ATP to N6-methyl-(d)AMP, followed by ADAL1-catalyzed deamination producing (d)IMP that can enter the nucleotide salvage pathway."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.ra120.012636"xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.ra120.012636"xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Stenmark P."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Stenmark P."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Braeutigam L."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Braeutigam L."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Helleday T."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Helleday T."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Jemth A.S."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Jemth A.S."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Sarno A."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Sarno A."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Scaletti E.R."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Scaletti E.R."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Vallin K.S."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Vallin K.S."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Warpman Berglund U."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/author | "Warpman Berglund U."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/32144205 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |