Abstract
SummarySurvival and genome stability are critical characteristics of healthy cells. DNA palindromes pose a threat to genome stability and have been shown to participate in a reaction leading to the formation of inverted chromosome duplications centered around themselves. There is considerable interest in the mechanism of this rearrangement given its likely contribution to genome instability in cancer cells. This study shows that formation of large inverted chromosome duplications can be observed in the chromosome of Escherichia coli. They are formed at the site of a 246 bp interrupted DNA palindrome in the absence of the hairpin nuclease SbcCD and the recombination protein RecA. The genetic requirements for this spontaneous rearrangement are consistent with a pathway involving DNA degradation and hairpin formation, as opposed to a cruciform cleavage pathway. Accordingly, the formation of palindrome-dependent hairpin intermediates can be induced by an adjacent DNA double-stand break.
Highlights
DNA palindromes are present at sites of genome instability
Detection of Novel DNA Fragments Induced by a DNA Palindrome in the Absence of SbcCD and RecA The behavior of a 246 bp interrupted palindrome in the lacZ gene of the E. coli chromosome was investigated by Southern blot analysis
Because expression of SbcCD is lethal in a recA mutant strain containing the 246 bp interrupted palindrome (Eykelenboom et al, 2008), it was not possible to use this palindrome to test whether the formation of these novel fragments requires the absence of SbcCD in a recA mutant
Summary
DNA palindromes are present at sites of genome instability. They are implicated in gene deletion, gene amplification, chromosome fracture, and chromosome translocation, aberrations characteristic of hereditary disease and rearrangements observed in cancer cells (Coteand Lewis, 2008; Lewis and Cote , 2006; Lobachev et al, 2007; Tanaka et al, 2005; Tanaka and Yao, 2009). A perfect palindrome is a DNA sequence that is immediately juxtaposed to an exact reverse complementary copy of itself, whereas an interrupted palindrome ( known as a closely spaced inverted repeat) contains a small unique sequence that separates the two inverted complementary copies (Lewis and Cote , 2006) Due to their symmetry, palindromes have the unique potential to form intrastrand base pairs in hairpin or cruciform DNA structures, and it is this potential that underlies their role in genomic instability (Lewis and Cote , 2006; Tanaka and Yao, 2009). This finding suggests that naturally occurring palindromes can play important roles in the formation of these gross chromosomal rearrangements, and evidence exists that natural palindromes may be causative of rearrangements observed in human cancers (Tanaka and Yao, 2009)
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