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Volume 272, Number 27,
Issue of July 4, 1997
pp. 16769-16777
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Evidence for a Unique Mechanism of Strand Transfer from the
Transactivation Response Region of HIV-1
(Received for publication, February 20, 1997, and in revised form, May 4, 1997)
Jin Kyung
Kim
,
Chockalingam
Palaniappan
,
Weimin
Wu
,
Philip J.
Fay
¶
and
Robert A.
Bambara

From the Departments of Biochemistry and Biophysics
and ¶ Medicine and the Cancer Center, University of
Rochester, Rochester, New York 14642
We previously found that strand transfer by human
immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is
promoted at sites where RT pauses during synthesis. In this report,
strand transfer is measured within the 5 transactivation response
region (TAR) of HIV-1 RNA. We hypothesized that the stable hairpin
structure of TAR would induce RT pausing, promoting RNase H-directed
cleavage of the template and subsequent transfer at that site. We
further predicted that HIV-1 nucleocapsid protein (NC), known to melt secondary structures, would decrease transfer. We show that TAR created
a strong pause site for RT, but NC significantly promoted strand
transfer. The effect of NC is specific, since other single strand
binding proteins failed to stimulate transfer. In another unexpected
outcome, preferred positions of internal transfer were not at the pause
site but were in the upper stem and loop of TAR. Thus, we propose a new
mechanism for transfer within TAR described by an interactive hairpin
model, in which association between the donor and the acceptor
templates within the TAR stem promotes transfer. The model is
consistent with the observed stimulation of strand transfer by NC. The
model is applicable to internal and replicative end transfer.

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Copyright © 1997 by the American Society for Biochemistry and Molecular Biology.
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