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

Transposable elements (transposons) are segments of DNA with the ability to move from one location into another within genomes. These ​“jumping genes” can be considered molecular parasites that use the resources of the host cell for their propagation. Transposons isolated from vertebrate species are generally inactive due to mutational damage that accumulated in them over evolutionary time. The Sleeping Beauty (SB) transposon, a reconstructed version of an ancient element in fish, was the first element of vertebrate origin that showed high transpositional activity in a variety of vertebrates. SB is a molecular tool for functional genomics in vertebrate models, a novel vector platform for human gene therapy, and a useful experimental system for the study of the fundamental biological questions concerning DNA transposition and its regulation in vertebrate cells.

Now, Oliver Walisko and colleagues (laboratory of Dr. Zoltán Ivics ) have used the SB element to probe transposon-host cell interactions (PNAS 2006, 103(11):4062 – 7) . The researchers identified the Miz‑1 transcription factor as an interactor of the SB transposase in a yeast two-hybrid screen. Through its association with Miz‑1, the SB transposase downregulates cyclin D1 expression in human cells, as evidenced by differential gene expression analysis using microarray hybridization. Downregulation of cyclin D1 results in a prolonged G1 phase of the cell-cycle and retarded growth of transposase-expressing cells. Both cyclin D1 downregulation and the G1 slowdown induced by the transposase require Miz‑1. A temporary G1 arrest enhances transposition, suggesting that Sleeping Beauty transposition is favored in the G1 phase of the cell-cycle, where the nonhomologous end joining (NHEJ) pathway of DNA repair is preferentially active. Because NHEJ is a limiting factor of SB transposition, the transposase-induced G1 slowdown is probably a ​“selfish act” on the transposon’s part to maximize the chance for a successful transposition event.

Contact:

Pamela Cohen
p.​cohen@​mdc-​berlin.​de
+49 30 9406 2121