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Molecular and Cellular Biology, December 2003, p. 8740-8750, Vol. 23, No. 23
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.23.8740-8750.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Rapid, Stabilizing Palindrome Rearrangements in Somatic Cells by the Center-Break Mechanism

Lesley A. Cunningham,1,2,{dagger} Atina G. Coté,2,3 Cennet Cam-Ozdemir,2 and Susanna M. Lewis2,3*

Department of Immunology,1 Department of Medical and Molecular Genetics, University of Toronto,3 Program in Genetics and Genomic Biology, Hospital for Sick Children Research Institute, Toronto, Canada2

Received 1 July 2003/ Returned for modification 11 August 2003/ Accepted 28 August 2003

DNA palindromes are associated with rearrangement in a variety of organisms. A unique opportunity to examine the impact of a long palindrome in mammals is afforded by the Line 78 strain of mice. Previously it was found that the transgene in Line 78 is likely to be palindromic and that the symmetry of the transgene was responsible for a high level of germ line instability. Here we prove that Line 78 mice harbor a true 15.4-kb palindrome, and through the establishment of cell lines from Line 78 mice we have shown that the palindrome rearranges at the impressive rate of about 0.5% per population doubling. The rearrangements observed to arise from rapid palindrome modification are consistent with a center-break mechanism where double-strand breaks, created through hairpin nicking of an extruded cruciform, are imprecisely rejoined, thus introducing deletions at the palindrome center. Significantly, palindrome rearrangements in somatic tissue culture cells almost completely mirrored the structures generated in vivo in the mouse germ line. The close correspondence between germ line and somatic events indicates the possibility that center-break modification of palindromes is an important mechanism for preventing mutation in both contexts. Permanent cell lines carrying a verified palindrome provide an essential tool for future mechanistic analyses into the consequences of palindromy in the mammalian genome.

* Corresponding author. Mailing address: Hospital for Sick Children Research Institute, 500 University Ave., Toronto, Ontario M5G 1X8, Canada. Phone: (416) 813-8980. Fax: (416) 813-8883. E-mail: Susanna{at}Sickkids.ca.

{dagger} Present address: Biology Department, York University, Toronto, Canada.

Molecular and Cellular Biology, December 2003, p. 8740-8750, Vol. 23, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.23.8740-8750.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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