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Studies unravel DNA replication

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You have more in common with E. coli than you may think. US researchers have demonstrated that DNA replication is triggered in exactly the same way whether you happen to be a bacterium, an archaeum or a eukaryote (that's modern bacteria, old bacteria, or cells with a nucleus, to you and me).

The Berkeley-based researchers identified the same structure at work in both bacterial and eukaryotic samples. The structure, identified as a "helical substructure within a super family of proteins called AAA+", was spotted doing its replication initiation thing in both E. coli bacteria, and in a humble fruit fly.

Previous research had identified this protein group as the culprit in archaea's replication, leading the various research teams to the conclusion that this trick must have evolved millions of years ago, before the three domains of life split off from one another.

"The ability of a cell to replicate its DNA in a timely and faithful manner is fundamental for survival," said Eva Nogales, a biophysicist from the fruit fly study.

"Despite decades of study, the structural and molecular basis for initiating DNA replication, and the degree to which these mechanisms have been conserved by evolution have been ill defined and hotly debated," she added.

Biochemist and structural biologist James Berger was involved in both studies. His team discovered that when a particular protein, DnaA, binds with adenosine triphosphate (ATP - a cell's energy source) it forces AAA+ proteins to unwind from their ring shape into a right-handed spiral.

This spiral in turn will wrap the double helix of DNA around itself, causing the DNA to deform, and begin the process of unzipping its two strands.

In the study of fruit flies, the researchers found the same mechanism at work. Although it has been known for some time that a protein complex called the origin recognition complex (ORC) initiates DNA replication in eukaryotes, not much was known about the structure of the initiator.

Now, thanks to the electron microscopy the group employed, it is clear that when bound to ATP, the ORC forms a helical structure that is very similar to that observed in the E. coli study.

Nogales says that although the data from the fruit flies doesn't actually show the DNA wrapped around the ORC, the similarities in structure that can be seen "suggests that there are likely to be strong mechanistic commonalities" between the two processes.

"The specialisation of DNA replication initiators took place a long time ago," NOgales concludes. "Through the millions of years, evolution has added bells and whistles around this highly conserved central engine."

Both studies will be published next month in the journal Nature Structural and Molecular Biology. ®

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