Sci. Aging Knowl. Environ., 24 October 2001
Protective Pas de Deux? A new partner might help Werner syndrome protein safeguard the genome during replication
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/abstract/sageke;2001/4/nw15
Key Words: Werner syndrome WRN FEN-1 DNA replication DNA repair nuclease helicase
Abstract: The protein that causes the premature aging disorder Werner syndrome (see "Of Hyperaging and Methuselah Genes") has picked up a fresh dance partner. The Werner syndrome protein (WRN) apparently enhances the moves of an enzyme that plays a role in DNA replication and repair. WRN was already known to bind to other proteins involved in these processes, and on its own, it unwinds and chews up DNA. But exactly what WRN does in the cell--and how its defective versions lead to premature aging--remains mysterious.
A protein called FEN-1 trims DNA tails that crop up during DNA replication and repair. In addition, the yeast version of FEN-1 helps maintain genetic stability; a defective form of it provokes genetic mayhem, such as large deletions, also seen in cells with faulty WRN. Because FEN-1 and WRN seem to inspire similar choreography, Brosh and colleagues wondered whether the two ever engage in a molecular tango. To find out, the researchers used a fragment of the WRN protein as bait to fish associated proteins out of material from human cell nuclei. Employing antibodies, they hauled WRN from the mixture and discovered that FEN-1 came along for the ride.
They then probed whether the union between the proteins affects their respective enzymatic activities. Although FEN-1 does not alter WRN's capacity to unwind DNA, WRN stimulates FEN-1's ability to cleave DNA: FEN-1 nibbles DNA faster when WRN is present than when FEN-1 tackles the chore by itself. Whether FEN-1 and WRN perform this duet in intact cells--and whether disrupting this collaboration is a critical trigger for Werner syndrome--remains to be seen. But the result offers a glimpse at some new variations in the Werner protein's repertoire.
--R. John Davenport; suggested by Matt Kaeberlein
R. M. Brosh Jr., C. von Kobbe, J. A. Sommers, P. Karmakar, P. L. Opresko, J. Piotrowski, I. Dianova, G. L. Dianov, V. A. Bohr, Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity. EMBO J. 20, 5791-5801 (2001). [Abstract] [Full Text]
Citation: R. J. Davenport, Protective Pas de Deux? A new partner might help Werner syndrome protein safeguard the genome during replication. Science's SAGE KE (24 October 2001), http://sageke.sciencemag.org/cgi/content/abstract/sageke;2001/4/nw15
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