SwePub
Sök i LIBRIS databas

  Extended search

onr:"swepub:oai:DiVA.org:su-181859"
 

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

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist
  • Scaletti, Emma RoseStockholm University,Lunds universitet,Stockholms universitet,Institutionen för biokemi och biofysik,Lund University, Sweden,Strukturell biokemi,Forskargrupper vid Lunds universitet,Structural Biochemistry,Lund University Research Groups (author)

MutT homologue 1 (MTH1) removes N6-methyl-dATP from the dNTP pool

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • 2020
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:su-181859
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-181859URI
  • https://doi.org/10.1074/jbc.RA120.012636DOI
  • https://lup.lub.lu.se/record/4bae637a-06af-4311-ad58-9cb5b8171c21URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:143498372URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Vallin, Karl S.Karolinska Institute (author)
  • Bräutigam, LarsKarolinska Institutet (author)
  • Sarno, AntonioKarolinska Institutet (author)
  • Warpman Berglund, UlrikaKarolinska Institutet,Karolinska Institute (author)
  • Helleday, ThomasKarolinska Institutet (author)
  • Stenmark, PålStockholm 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 Groups(Swepub:lu)pa4463st (author)
  • Jemth, Ann-SofieKarolinska Institute (author)
  • Stockholms universitetInstitutionen för biokemi och biofysik (creator_code:org_t)

Related titles

  • In:Journal of Biological Chemistry295:15, s. 4761-47720021-92581083-351X

Internet link

Find in a library

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view