Study shows DNA acts like Ômagic ringsÕ trick Davis Enterprise Page 1 of 5

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Study shows DNA acts like Recent Posts Ômagic ringsÕ trick A big thanks to the dads Print edition, Sunday, June 16, 2013 By Andy Fell October 19, 2010 | Leave Comment River Cats shut down Tacoma Wire sports briefs: Bruins tie Cup finals in OT Special to the Enterprise Sports briefs: Hicks injured at UCLA football camp; to miss final DHS season A new study from UC Davis shows how, like a conjuring trick with interlocking rings, two interlocked pieces of DNA are separated after DNA is copied or repaired.

While reconstituting the DNA repair system of yeast in a test tube, the researchers found that a complex of proteins called Search Sgs1, Top3 and Rmi1 allow one DNA strand to open and the other to pass through. HOME ÒThis protein complex does what magicians do,Ó said lead NEWS researcher Stephen Kowalczykowski, distinguished professor FORUM of microbiology in the UCD College of Biological Sciences and SPORTS a member of the UCD Cancer Center.

FEATURES The finding was published online Oct. 10 in the journal Nature ARTS Structural and Molecular Biology.

BUSINESS The discovery may hold answers to a human disease called OBITUARIES BloomÕs syndrome, which increases the risk of cancer, among COMICS other health problems. Sgs1 appears to be the yeast equivalent of the human protein tied to BloomÕs syndrome, GALLERY Kowalczykowski said. CLASSIFIEDS DNA suffers damage all the time both from outside influences, ADVERTISERS such as radiation or chemicals, and also from normal cellular CONTACT US processes. Unrepaired, DNA damage can lead to cancer or birth defects. Several genes linked to a high risk of cancer, such as the Òbreast cancer geneÓ BRCA2, have turned out to be involved in DNA repair.

When damage crosses both strands of the DNA double helix, a sophisticated repair process is activated that uses the same DNA sequence on the matching chromosome. One of the 1,892 2,299 strands is stripped back, leaving an exposed single strand. The matching chromosome is brought alongside and partly unwound, and acts as a template to repair the broken piece.

At this point, the two chromosomes are intact but attached at two points through structures called ÒHolliday junctions,Ó where DNA strands from the two chromosomes cross each other. To finish the process, the chromosomes have to separate Ñ like the magicianÕs interlocking rings, one has to pass through the other.

Working with a mix of yeast proteins and DNA in a test tube, Kowalczykowski and his colleagues showed that the Sgs1/Top3/Rmi1 protein complex attaches to the paired DNA at the Holliday junction, opens up a gap in one strand and passes the other through it, allowing the two chromosomes to separate cleanly and dissolving the junction.

Patients with BloomÕs syndrome show extensive swapping of chunks of DNA between chromosomes. Kowalczykowski is convinced that the problem is due to poor dissolution of Holliday junctions in these patients.

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Holliday junctions were only definitively shown to exist in mitotically dividing cells in April this year, in a paper by UCD researchers Malgosia Bzymek and Neil Hunter, associate professor of microbiology.

KowalczykowskiÕs collaborators in the new study were UCS postdoctoral researchers Petr Cejka and Jody Plank, and Oxford University scientists Csanad Bachrati and Ian Hickson.

In a paper published in Nature last month, KowalczykowskiÕs lab also showed that the Sgs1/Top3/Rmi1 complex of proteins is involved in the first step of DNA repair Ñ cleaning the broken end to leave a single strand of DNA.

The research was funded by the National Institutes of Health, the Swiss National Science Foundation and Cancer Research UK.

Ñ UC Davis News Service

Andy Fell

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