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Sökning: onr:"swepub:oai:DiVA.org:su-181859" > MutT homologue 1 (M...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005539naa a2200673 4500
001oai:DiVA.org:su-181859
003SwePub
008200527s2020 | |||||||||||000 ||eng|
009oai:lup.lub.lu.se:4bae637a-06af-4311-ad58-9cb5b8171c21
009oai:prod.swepub.kib.ki.se:143498372
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1818592 URI
0247 a https://doi.org/10.1074/jbc.RA120.0126362 DOI
0247 a https://lup.lub.lu.se/record/4bae637a-06af-4311-ad58-9cb5b8171c212 URI
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1434983722 URI
040 a (SwePub)sud (SwePub)lud (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Scaletti, Emma Roseu Stockholm University,Lunds universitet,Stockholms universitet,Institutionen för biokemi och biofysik,Lund University, Sweden,Strukturell biokemi,Forskargrupper vid Lunds universitet,Structural Biochemistry,Lund University Research Groups4 aut0 (Swepub:lu)em4772sc
2451 0a MutT homologue 1 (MTH1) removes N6-methyl-dATP from the dNTP pool
264 1c 2020
338 a print2 rdacarrier
520 a 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.
650 7a NATURVETENSKAPx Biologi0 (SwePub)1062 hsv//swe
650 7a NATURAL SCIENCESx Biological Sciences0 (SwePub)1062 hsv//eng
650 7a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe
650 7a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinsk bioteknologix Medicinsk bioteknologi0 (SwePub)304012 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Medical Biotechnologyx Medical Biotechnology0 (SwePub)304012 hsv//eng
653 a crystal structure
653 a X-ray crystallography
653 a enzyme catalysis
653 a substrate specificity
653 a enzyme kinetics
653 a nucleoside
653 a nucleotide metabolism
653 a hydrolase
653 a epigenetics
653 a methylation
653 a MutT homologue 1 (MTH1)
653 a N6-methyl-dATP
653 a nucleotide hydrolysis
653 a Nudix hydrolase 1 (NUDT1)
7001 a Vallin, Karl S.u Karolinska Institute4 aut
7001 a Bräutigam, Larsu Karolinska Institutet4 aut
7001 a Sarno, Antoniou Karolinska Institutet4 aut
7001 a Warpman Berglund, Ulrikau Karolinska Institutet,Karolinska Institute4 aut
7001 a Helleday, Thomasu Karolinska Institutet4 aut
7001 a Stenmark, Pålu Stockholm University,Lunds universitet,Stockholms universitet,Institutionen för biokemi och biofysik,Lund University, Sweden,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Strukturell biokemi,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Structural Biochemistry,Lund University Research Groups4 aut0 (Swepub:lu)pa4463st
7001 a Jemth, Ann-Sofieu Karolinska Institute4 aut
7102 a Stockholms universitetb Institutionen för biokemi och biofysik4 org
7730 t Journal of Biological Chemistryg 295:15, s. 4761-4772q 295:15<4761-4772x 0021-9258x 1083-351X
8564 u https://doi.org/10.1074/jbc.RA120.012636y Fulltext
8564 u http://dx.doi.org/10.1074/jbc.RA120.012636x freey FULLTEXT
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-181859
8564 8u https://doi.org/10.1074/jbc.RA120.012636
8564 8u https://lup.lub.lu.se/record/4bae637a-06af-4311-ad58-9cb5b8171c21
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:143498372

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