Adeno-associated virus site-specific integration is regulated by TRP-185.

Abstract:

:Adeno-associated virus (AAV) integrates site specifically into the AAVS1 locus on human chromosome 19. Although recruitment of the AAV nonstructural protein Rep78/68 to the Rep binding site (RBS) on AAVS1 is thought to be an essential step, the mechanism of the site-specific integration, particularly, how the site of integration is determined, remains largely unknown. Here we describe the identification and characterization of a new cellular regulator of AAV site-specific integration. TAR RNA loop binding protein 185 (TRP-185), previously reported to associate with human immunodeficiency virus type 1 TAR RNA, binds to AAVS1 DNA. Our data suggest that TRP-185 suppresses AAV integration at the AAVS1 RBS and enhances AAV integration into a region downstream of the RBS. TRP-185 bound to Rep68 directly, changing the Rep68 DNA binding property and stimulating Rep68 helicase activity. We present a model in which TRP-185 changes the specificity of the AAV integration site from the RBS to a downstream region by acting as a molecular chaperone that promotes Rep68 complex formation competent for 3'-->5' DNA helicase activity.

journal_name

J Virol

journal_title

Journal of virology

authors

Yamamoto N,Suzuki M,Kawano MA,Inoue T,Takahashi RU,Tsukamoto H,Enomoto T,Yamaguchi Y,Wada T,Handa H

doi

10.1128/JVI.02014-06

subject

Has Abstract

pub_date

2007-02-01 00:00:00

pages

1990-2001

issue

4

eissn

0022-538X

issn

1098-5514

pii

JVI.02014-06

journal_volume

81

pub_type

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