While tracing the origin of this extra DNA, Daria Babushok, an MD/PhD student in the Kazazian lab, came up with the missing steps in the mechanism of retrotransposon replication. "It was known previously that the enzyme endonuclease cleaves one of the strands of cellular DNA and then the retrotransposon inserts by binding to that cleaved DNA strand and copying itself onto that strand," she says. "It sneaks in there."
How the retrotransposon finally integrated and pasted itself back together was unknown, until this paper. "What we saw in our insertions hinted at the possibility that reverse transcriptase actually jumps onto the second DNA strand and continues the synthesis," she explains. "We think that this is how the second part of the element integrates into the genome. If this mechanism proves to be correct, it will bring us much closer to knowing how more than half a million retrotransposons have accumulated in the human genome."
Eventually, continuous jumping by retrotransposons expands the size of the human genome and may cause shuffling of genome content. For example, when retrotransposons jump, they may take portions of nearby gene sequences with them, inserting these where they land, and thereby allowing for the creation of new genes. Even otherwise unremarkable insertions of L1 may cause significant effects on nearby genes, such as lowering their expression.
Now, by knowing the final steps in retrotransposon replication and being able to follow and map new insertions in animals, the researchers will be able to more fully understand how L1 retrotransposons are able to invade the human genome.
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
31-Jan-2006