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Clearing Jams In Copy Machinery

Date:
September 20, 2005
Source:
Rockefeller University
Summary:
Rockefeller University scientists show that a protein crucial for the accurate copying of DNA during cell division serves as a toolbelt from which the correct proteins are retrieved to enable DNA replication in the face of DNA damage.
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Bacteria and humans use a number of tools to direct perhapsthe most important function in cells -- the accurate copying of DNAduring cell division. New research published this week in MolecularCell from the laboratory of Rockefeller University's Michael O'Donnell,a Howard Hughes Medical Institute Investigator, now shows that one ofthese proteins, the beta sliding clamp, serves as a toolbelt from whichthe correct proteins are retrieved to enable DNA replication in theface of DNA damage.

The replication machinery inside the cell'snucleus is made up of a collection of enzymes including DNApolymerases, sliding clamps and clamp loaders. Bacteria have five knownDNA polymerases (higher organisms such as humans have more). As thering-shaped beta sliding clamp works its way along the DNA doublehelix, a network of proteins work together to unwind the two strands.Polymerases then add, in assembly line fashion, nucleotide bases -- thebuilding blocks that make up DNA -- to convert the now-single-strandedtemplates into two new duplex DNA molecules.

The new researchshows that two different DNA polymerases, the high fidelity Pol IIIreplicase and the low fidelity Pol IV, coordinate their action to crossobstacles encountered in the replication process. They attachthemselves at the same time to one beta sliding clamp. Pol III copiesthe original DNA, and acts as a proofreader to catch any misspellingsand cuts any base that is wrong. But Pol III is a perfectionist, andcan stall if it encounters a problem. Pol IV, on the other hand, laysdown bases without checking for errors, keeping the process moving evenwhen Pol III gets stuck. The findings by O'Donnell and his colleaguesshow that, because both polymerases are bound simultaneously to thebeta clamp, it can pull either of the polymerases out if its toolbeltas needed.

O'Donnell and his colleagues propose two explanations for how the polymerase switch is controlled.

"Onepossibility is that the beta clamp may sense when Pol III stalls,triggering a change in beta that pulls the polymerase from the primedsite, allowing Pol IV to take over synthesis," O'Donnell says. Or, PolIII, upon stalling, may loosen its grip on the template and allow PolIV to bind the primed site instead.

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Molecular Cell 19(6):805-814 (2005)


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Rockefeller University. "Clearing Jams In Copy Machinery." ScienceDaily. ScienceDaily, 20 September 2005. <www.sciencedaily.com/releases/2005/09/050920082649.htm>.
Rockefeller University. (2005, September 20). Clearing Jams In Copy Machinery. ScienceDaily. Retrieved March 29, 2024 from www.sciencedaily.com/releases/2005/09/050920082649.htm
Rockefeller University. "Clearing Jams In Copy Machinery." ScienceDaily. www.sciencedaily.com/releases/2005/09/050920082649.htm (accessed March 29, 2024).

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