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Sleeping Beauty transposase modulates cell-cycle progression through interaction with Miz-1

Item Type:Article
Title:Sleeping Beauty transposase modulates cell-cycle progression through interaction with Miz-1
Creators Name:Walisko, O. and Izsvak, Z. and Szabo, K. and Kaufman, C.D. and Herold, S. and Ivics, Z.
Abstract:We used the Sleeping Beauty (SB) transposable element as a tool to probe transposon-host cell interactions in vertebrates. The Miz-1 transcription factor was identified as an interactor of the SB transposase in a yeast two-hybrid screen. Through its association with Miz-1, the SB transposase down-regulates cyclin D1 expression in human cells, as evidenced by differential gene expression analysis using microarray hybridization. Down-regulation of cyclin D1 results in a prolonged G(1) phase of the cell cycle and retarded growth of transposase-expressing cells. G(1) slowdown is associated with a decrease of cyclin D1/cdk4-specific phosphorylation of the retinoblastoma protein. Both cyclin D1 down-regulation and the G(1) slowdown induced by the transposase require Miz-1. A temporary G(1) arrest enhances transposition, suggesting that SB transposition is favored in the G(1) phase of the cell cycle, where the nonhomologous end-joining pathway of DNA repair is preferentially active. Because nonhomologous end-joining is required for efficient SB transposition, the transposase-induced G(1) slowdown is probably a selfish act on the transposon's part to maximize the chance for a successful transposition event.
Keywords:Cyclin D1, Protein–Protein Interaction, Transposition, Animals
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:103
Number:11
Page Range:4062-4067
Date:14 March 2006
Official Publication:https://doi.org/10.1073/pnas.0507683103
PubMed:View item in PubMed

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