GAPF profiles from HFF2 and Colo320DM cells

Amplification of large chromosomal regions (gene amplification) is a common somatic alteration in human cancer cells and often is associated with advanced disease. A critical event initiating gene amplification is a DNA double strand break (DSB), which is immediately followed by the formation of a large DNA palindrome. Large DNA palindromes are frequent and non-randomly distributed in the genomes of cancer cells and facilitate further increase in copy number. Although the importance of the formation of large DNA palindromes as a very early event in gene amplification is widely recognized, it is not known 1) how a DSB is resolved to form a large DNA palindrome; and 2) whether any local DNA structure determines the location of large DNA palindromes. We show here that intra-strand annealing following a DNA double-strand break leads to the formation of large DNA palindromes and that DNA inverted repeats in the genome determines the efficiency of this event. Furthermore, in human Colo320DM cancer cells, a DNA inverted repeat in the genome marks the border between amplified and non-amplified DNA. Therefore, an early step of gene amplification is a regulated process that is facilitated by DNA inverted repeats in the genome.

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Tanaka H, Cao Y, Bergstrom DA, Kooperberg C, Tapscott SJ, Yao MC