Publications
2006
Goldschmidt V, Didierjean J, Ehresmann B, Ehresmann C, Isel C, Marquet R
Mg2+ dependency of HIV-1 reverse transcription, inhibition by nucleoside analogues and resistance Article de journal
Dans: Nucleic Acids Res, vol. 34, no. 1, p. 42-52, 2006, ISBN: 16394022, (1362-4962 (Electronic) Journal Article).
Résumé | Liens | BibTeX | Étiquettes: Adenosine Triphosphate/pharmacology Anti-HIV Agents/*pharmacology DNA/biosynthesis DNA Primers DNA, Calf Thymus/metabolism Zidovudine/pharmacology, MARQUET, Non-U.S. Gov't Reverse Transcriptase Inhibitors/*pharmacology *Reverse Transcription/drug effects Ribonuclease H, PAILLART, Single-Stranded/biosynthesis Drug Resistance, Unité ARN, Viral HIV-1 Reverse Transcriptase/*metabolism Magnesium/*pharmacology Nucleosides/pharmacology Research Support
@article{,
title = {Mg2+ dependency of HIV-1 reverse transcription, inhibition by nucleoside analogues and resistance},
author = {V Goldschmidt and J Didierjean and B Ehresmann and C Ehresmann and C Isel and R Marquet},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16394022},
isbn = {16394022},
year = {2006},
date = {2006-01-01},
journal = {Nucleic Acids Res},
volume = {34},
number = {1},
pages = {42-52},
abstract = {Metal ions are essential for DNA polymerase and RNase H activities of HIV-1 reverse transcriptase (RT). RT studies are routinely performed at 6-8 mM Mg2+, despite the fact that the in vivo concentration might be as low as 0.2 mM. We studied the influence of MgCl2 and ATP, which likely binds a significant fraction of the magnesium pool in vivo, on the DNA polymerase and RNase H activities of HIV-1 RT, its inhibition by nucleoside RT inhibitors (NRTIs) and primer unblocking by AZT-resistant RT. At low Mg2+ concentration, reverse transcription of a natural template strongly increased despite a dramatically reduced intrinsic polymerase activity under such conditions. Low Mg2+ concentrations affected the RNA stability and indirectly decreased its degradation by the RNase H activity. The reduced RNA degradation prevented premature dissociation of the template and primer strands that otherwise generated dead-end DNA products. In addition, low Mg2+ dramatically decreased the incorporation of NRTIs into DNA and increased nucleotide excision by AZT-resistant RT. The latter effect is also most likely owing to the diminished cleavage of the RNA template. Thus, differences in the free Mg2+ concentration between different cell types or during the cell cycle might strongly affect HIV-1 replication and its inhibition.},
note = {1362-4962 (Electronic)
Journal Article},
keywords = {Adenosine Triphosphate/pharmacology Anti-HIV Agents/*pharmacology DNA/biosynthesis DNA Primers DNA, Calf Thymus/metabolism Zidovudine/pharmacology, MARQUET, Non-U.S. Gov't Reverse Transcriptase Inhibitors/*pharmacology *Reverse Transcription/drug effects Ribonuclease H, PAILLART, Single-Stranded/biosynthesis Drug Resistance, Unité ARN, Viral HIV-1 Reverse Transcriptase/*metabolism Magnesium/*pharmacology Nucleosides/pharmacology Research Support},
pubstate = {published},
tppubtype = {article}
}