Inhibition of reverse transcription in vivo by elevated manganese ion concentration

Eric C. Bolton, Albert S. Mildvan, Jef D. Boeke

Research output: Contribution to journalArticlepeer-review

Abstract

Mutations in PMR1, a yeast gene encoding a calcium/manganese exporter, dramatically decrease Ty1 retro-transposition. Ty1 cDNA is reduced in pmr1 mutant cells, despite normal levels of Ty1 RNA and proteins. The transposition defect results from Mn2+ accumulation that inhibits reverse transcription. Cytoplasmic accumulation of Mn2+ in pmr1 cells may directly affect reverse transcriptase (RT) activity. Trace amounts of Mn2+ potently inhibit Ty1 RT and HIV-1 RT in vitro when the preferred cation, Mg2+, is present. Both Mn2+ and Mg2+ alone activate Ty1 RT cooperatively with Hill coefficients of 2, providing kinetic evidence for a dual divalent cation requirement at the RT active site. We propose that occupancy of the B site is the major determinant of catalytic activity and that Mn2+ at this site greatly reduces catalytic activity.

Original languageEnglish (US)
Pages (from-to)879-889
Number of pages11
JournalMolecular cell
Volume9
Issue number4
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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