期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：46
页码：13003-13008
DOI：10.1073/pnas.1613508113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe P-element transposon is a mobile DNA that invaded the Drosophila genome approximately 100 y ago. P elements were identified by studying a genetic syndrome called "hybrid dysgenesis." The elements use their encoded transposase for mobility, but rely on host-cell factors for essential parts of their life cycle. Here we demonstrate biochemically that a Drosophila-encoded bZIP heterodimer binds to the P-element terminal 31-bp sequences. We used genetics to show that these proteins play a role in repairing DNA breaks caused by P-element transposase activity during hybrid dysgenesis and other types of DNA damage. These results provide an example of the mechanisms that the host genome uses to combat genome instability caused by foreign DNA invasion. In Drosophila, P-element transposition causes mutagenesis and genome instability during hybrid dysgenesis. The P-element 31-bp terminal inverted repeats (TIRs) contain sequences essential for transposase cleavage and have been implicated in DNA repair via protein-DNA interactions with cellular proteins. The identity and function of these cellular proteins were unknown. Biochemical characterization of proteins that bind the TIRs identified a heterodimeric basic leucine zipper (bZIP) complex between an uncharacterized protein that we termed "Inverted Repeat Binding Protein (IRBP) 18" and its partner Xrp1. The reconstituted IRBP18/Xrp1 heterodimer binds sequence-specifically to its dsDNA-binding site within the P-element TIRs. Genetic analyses implicate both proteins as critical for repair of DNA breaks following transposase cleavage in vivo. These results identify a cellular protein complex that binds an active mobile element and plays a more general role in maintaining genome stability.
关键词：P-transposable elements ; DNA repair ; IRBP18/CG6272 ; Xrp1/CG17836 ; IRBP complex
