Sleeping Beauty and DNA-Repair

Dr. Izsvák and Dr. Ivics used an artificial transposable
DNA element which they constructed a few years ago and named Sleeping Beauty.
It has since proven to be an excellent tool to study DNA repair. Transposable
DNA elements (transposons) can be found in the genomes of most living
organisms, ranging from bacteria to humans. However, they are very rare in
human disease as they became inactivated by mutations during evolution. Sleeping
Beauty is based on ancient
genomic elements from fish that are presumed to have been active approximately
20 million years ago. By cutting out all mutations in the transposon, Sleeping
Beauty has been literally “awakened with a kiss”, hence the name. It is
made up of two components: the transposable DNA (or transposon) and a protein
factor (the transposase) necessary to insert the transposable element into the
host cell´s DNA.

During the
early steps of transposition, Sleeping Beauty is cut out from the DNA,
thereby causing the DNA double-strand to break into two parts. Dr. Izsvák and
Dr. Ivics were able to show that two major pathways of the cell machinery
contribute to the repair of such DNA damage: one that relies on the presence of
DNA that is homologous (i.e., it has the same sequence) to the site where the
break occurred, and the other that is independent of homology. This was
an unexpected finding because immunoglobulin gene recombination (a
transposition-like process responsible for generating antibody diversity in the
immune system) was previously shown to be solely dependent on non-homologous
repair pathways. Repair of transposon-generated DNA breaks has been studied
primarily in the fruitfly, Drosophila melanogaster. Now, using the Sleeping
Beauty element as an experimental tool in mammalian cells, the authors
identified a protein called Xrcc3, hitherto unknown to play a role in
transposition. The findings provide
important clues about differential regulation of transposition and other DNA recombination mechanisms and expand our understanding
of the principal molecular processes involved in cellular responses to DNA
damage in mammalian cells.

Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC)
Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax:  +49 (0) 30
94 06 - 38 33
e-mail: presse@mdc-berlin.de
http://www.mdc-berlin.de/englisch/about_the_mdc/public_relations/e_index.htm