DNA and the 'magic rings' trickOctober 11, 2010
(PhysOrg.com) -- 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. The finding was published online Oct. 10 in the journal Nature Structural and Molecular Biology.
While reconstituting the DNA repair system of yeast in a test tube, the researchers found that a complex of proteins called Sgs1, Top3 and Rmi1 allow one DNA strand to open and the other to pass through.
"This protein complex does what magicians do," said lead researcher Stephen Kowalczykowski, distinguished professor of microbiology in the UC Davis College of Biological Sciences and a member of the of the UC Davis Cancer Center.
The discovery may hold answers to a human disease called Bloom's syndrome, which increases the risk of cancer, among other health problems. Sgs1 appears to be the yeast equivalent of the human protein tied to Bloom's syndrome, Kowalczykowski said.
DNA suffers damage all the time both from outside influences, such as radiation or chemicals, and also from normal cellular processes. Unrepaired,DNA damage can lead to cancer or birth defects. Several genes linked to a high risk of cancer, such as the "breast cancer gene" 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 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.
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Nature Structural & Molecular Biology
Published online: 10 October 2010 | doi:10.1038/nsmb.1919
Rmi1 stimulates decatenation of double Holliday junctions during dissolution by Sgs1–Top3
Petr Cejka1,3, Jody L Plank1,3, Csanad Z Bachrati2, Ian D Hickson2 & Stephen C Kowalczykowski1
Abstract
A double Holliday junction (dHJ) is a central intermediate of homologous recombination that can be processed to yield crossover or non-crossover recombination products. To preserve genomic integrity, cells possess mechanisms to avoid crossing over. We show that Saccharomyces cerevisiae Sgs1 and Top3 proteins are sufficient to migrate and disentangle a dHJ to produce exclusively non-crossover recombination products, in a reaction termed “dissolution.” We show that Rmi1 stimulates dHJ dissolution at low Sgs1–Top3 protein concentrations, although it has no effect on the initial rate of Holliday junction (HJ) migration. Rmi1 serves to stimulate DNA decatenation, removing the last linkages between the repaired and template DNA molecules. Dissolution of a dHJ is a highly efficient and concerted alternative to nucleolytic resolution that prevents crossing over of chromosomes during recombinational DNA repair in mitotic cells and thereby contributes to genomic integrity.
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Stephen Kowalczykowski, professor de microbiologia na Universidade da Califórnia-Davis, salientou:
“This protein complex does what magicians do... To finish the process, the chromosomes have to separate – like the magician’s interlocking rings, one has to pass through the other.”
Mágica ou Design Inteligente???
