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M94A0065.TXT
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1994-10-01
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Document 0065
DOCN M94A0065
TI HIV-1 reverse transcription. A termination step at the center of the
genome.
DT 9412
AU Charneau P; Mirambeau G; Roux P; Paulous S; Buc H; Clavel F; Unite
d'Oncologie Virale, CNRS URA 1157, Institut Pasteur,; Paris, France.
SO J Mol Biol. 1994 Sep 2;241(5):651-62. Unique Identifier : AIDSLINE
MED/94351714
AB During HIV-1 reverse transcription, the plus-strand of viral DNA is
synthesized as two discrete segments. We show here that synthesis of the
upstream segment terminates at the center of the genome after an 88 or
98 nucleotide strand displacement of the downstream segment, initiated
at the central polypurine tract. Thus, the final structure of
unintegrated linear HIV-1 DNA includes a central plus-strand overlap. In
vitro reconstitution using only purified reverse transcriptase with
appropriate DNA hybrids gave rise to efficient and accurate termination,
which was dramatically amplified in the context of strand displacement.
Mutation of the sequence immediately upstream of the termination sites
almost completely abolished termination both in infected cells and in
vitro. This mutation profoundly impaired replication of HIV-1. We
conclude that proper central plus-strand termination, mediated by a
novel cis-active termination sequence, is a key step in HIV-1
replication.
DE Base Sequence Cell Line, Transformed Conserved Sequence DNA,
Viral/BIOSYNTHESIS Human HIV-1/*GENETICS Models, Genetic Molecular
Sequence Data Mutagenesis, Site-Directed Reverse
Transcriptase/*METABOLISM RNA, Viral/*GENETICS Sequence Analysis, DNA
Support, Non-U.S. Gov't Terminator Regions (Genetics)/*GENETICS
Transcription, Genetic/*PHYSIOLOGY Virus Replication/PHYSIOLOGY
JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).