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 Viroljournal_title
Journal of virologyauthors
Yamamoto N,Suzuki M,Kawano MA,Inoue T,Takahashi RU,Tsukamoto H,Enomoto T,Yamaguchi Y,Wada T,Handa Hdoi
10.1128/JVI.02014-06subject
Has Abstractpub_date
2007-02-01 00:00:00pages
1990-2001issue
4eissn
0022-538Xissn
1098-5514pii
JVI.02014-06journal_volume
81pub_type
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