Controlling integration specificity of a yeast retrotransposon.

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.

authors

Zhu Y,Dai J,Fuerst PG,Voytas DF

doi

10.1073/pnas.1036705100

keywords:

subject

Has Abstract

pub_date

2003-05-13 00:00:00

pages

5891-5

issue

10

eissn

0027-8424

issn

1091-6490

pii

1036705100

journal_volume

100

pub_type

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