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Nonhomologous DNA end rejoining in chromosomal aberration formation
Affiliation:1. Department of Management and Marketing, Faculty of Business and Economics, 198 Berkeley Street, The University of Melbourne, Victoria 3010, Australia;2. Monash Business School, Monash University, Wellington Rd, Clayton, Victoria 3800, Australia; and Faculty of Business and Economics, University of Auckland, Auckland 1010, New Zealand;3. Newcastle Business School, The University of Newcastle, Ourimbah, New South Wales 2308, Australia;4. Project Owner – Design Thinking and Innovation, Motius GmbH, Walter-Gropius-Straße 17, 80807 München, Germany;1. Forschungszentrum Jülich GmbH, Institute for Energy and Climate Research, IEK-2, 52425 Jülich, Germany;2. Technische Universität Kaiserslautern, Lehrstuhl für Werkstoffkunde (WKK), 67663 Kaiserlautern, Germany
Abstract:The role of recombination of nonhomologous DNA ends in chromosomal aberration formation was investigated in Chinese hamster ovary cells. Restriction enzymes that produce blunt, 3′ overhanging, or 5′ overhanging DNA double-strand breaks were electroporated into cells in various combinations, and chromosomal aberrations were analyzed at metaphase. For all enzyme combinations tested, there was a significant increase in the frequency of aberrations whose formation requires two breaks in the DNA over the sum obtained when each of the enzymes was tested separately and the aberration frequencies were totaled. No such pattern existed for terminal deletions, which presumably require only one DNA break. The extent of interaction did not depend on the homology in the overhanging sequences or on the combination of ends used, although the largest effect was seen with a combination of two blunt ends. This study shows that nonhomologous DNA double-strand breaks can interact to increase chromosomal aberration formation significantly.
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