Abstract:
:Retrotransposons and retroviruses integrate nonrandomly into eukaryotic genomes. For the yeast retrotransposon Ty5, integration preferentially occurs within domains of heterochromatin. Targeting to these locations is determined by interactions between an amino acid sequence motif at the C terminus of Ty5 integrase (IN) called the targeting domain, and the heterochromatin protein Sir4p. Here we show that new Ty5 integration hot spots are created when Sir4p is tethered to ectopic DNA sites. Targeting to sites of tethered Sir4p is abrogated by single amino acid substitutions in either IN or Sir4p that prevent their interaction. Ty5 target specificity can be altered by replacing the IN-targeting domain with other peptide motifs that interact with known protein partners. Integration occurs at high efficiency and in close proximity to DNA sites where the protein partners are tethered. These findings define a mechanism by which retrotransposons shape their host genomes and suggest ways in which retroviral integration can be controlled.
journal_name
Proc Natl Acad Sci U S Aauthors
Zhu Y,Dai J,Fuerst PG,Voytas DFdoi
10.1073/pnas.1036705100keywords:
subject
Has Abstractpub_date
2003-05-13 00:00:00pages
5891-5issue
10eissn
0027-8424issn
1091-6490pii
1036705100journal_volume
100pub_type
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