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J. Biol. Chem., Vol. 276, Issue 16, 12827-12831, April 20, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/16/12827    most recent M010906200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hashimoto, M. Articles by Kow, Y. W. Search for Related Content PubMed PubMed Citation Articles by Hashimoto, M. Articles by Kow, Y. W. Social Bookmarking                      What's this?

A Possible Role of Ku in Mediating Sequential Repair of Closely Opposed Lesions^*

Mitsumasa Hashimoto, Carlton D. Donald, Steven M. Yannone^§, David J. Chen^§, Robindra Roy^¶, and Yoke W. Kow

From the  Department of Radiation Oncology, Emory University, Atlanta, Georgia 30335, the ^§ Lawrence Berkeley National Laboratory, Berkeley, California 94720 and the ^¶ Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555

One of the hallmarks of ionizing radiation exposure is the formation of clustered damage that includes closely opposed lesions. We show that the Ku70/80 complex (Ku) has a role in the repair of closely opposed lesions in DNA. DNA containing a dihydrouracil (DHU) close to an opposing single strand break was used as a model substrate. It was found that Ku has no effect on the enzymatic activity of human endonuclease III when the substrate DNA contains only DHU. However, with DNA containing a DHU that is closely opposed to a single strand break, Ku inhibited the nicking activity of human endonuclease III as well as the amount of free double strand breaks induced by the enzyme. The inhibition on the formation of a free double strand break by Ku was found to be much greater than the inhibition of human endonuclease III-nicking activity by Ku. Furthermore, there was a concomitant increase in the formation of Ku-DNA complexes when endonuclease III was present. Similar results were also observed with Escherichia coli endonuclease III. These results suggest that Ku reduces the formation of endonuclease III-induced free double strand breaks by sequestering the double strand breaks formed as a Ku-DNA complex. In doing so, Ku helps to avoid the formation of the intermediary free double strand breaks, possibly helping to reduce the mutagenic event that might result from the misjoining of frank double strand breaks.

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