Frequency of deletion formation decreases exponentially with distance between short direct repeats

Chédin, Frédéric; Dervyn, Etienne; Dervyn, Rozenn; Ehrlich, S. Dusko; Noirot, Ph.

doi:10.1111/j.1365-2958.1994.tb01042.x

Cited by 72 publications

(61 citation statements)

References 56 publications

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“…Moreover, proximity of the repeat sequences clearly plays an essential role in RecA-independent recombination. There is an exponential decrease in deletion rate as the distance between the homologies increases (11,21,41). This contrasts to RecA-dependent recombination of tandem repeats that shows little proximity effect (21).…”

Section: Resultsmentioning

confidence: 56%

Instability of repetitive DNA sequences: The role of replication in multiple mechanisms

Bzymek

Lovett

2001

Proc. Natl. Acad. Sci. U.S.A.

328

258

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Rearrangements between tandem sequence homologies of various lengths are a major source of genomic change and can be deleterious to the organism. These rearrangements can result in either deletion or duplication of genetic material flanked by direct sequence repeats. Molecular genetic analysis of repetitive sequence instability in Escherichia coli has provided several clues to the underlying mechanisms of these rearrangements. We present evidence for three mechanisms of RecA-independent sequence rearrangements: simple replication slippage, sister-chromosome exchange-associated slippage, and single-strand annealing. We discuss the constraints of these mechanisms and contrast their properties with RecA-dependent homologous recombination. Replication plays a critical role in the two slipped misalignment mechanisms, and difficulties in replication appear to trigger rearrangements via all these mechanisms.

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Section: Resultsmentioning

confidence: 56%

Instability of repetitive DNA sequences: The role of replication in multiple mechanisms

Bzymek

Lovett

2001

Proc. Natl. Acad. Sci. U.S.A.

328

258

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“…6). Similar frequencies of excision in E. coli were also estimated using a variant (Ché din et al, 1994) of the fluctuation test first described by Luria and Delbrü ck (1943) (data not shown). Significantly, excision at HIP1 sites occurred at a similar frequency (c. 1.5 in 10 8 cells) in both E. coli and Synechococcus PCC 7942 (Fig.…”

Section: ¹99mentioning

confidence: 99%

HIP1 propagates in cyanobacterial DNA via nucleotide substitutions but promotes excision at similar frequencies in Escherichia coli and Synechococcus PCC 7942

Robinson

Cranenburgh

Head

et al. 1997

Molecular Microbiology

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SummaryThe sequence 5Ј-GCGATCGC-3Ј, designated HIP1, for highly iterated palindrome, was first identified at the borders of a gene-deletion event and subsequently shown to constitute up to 2.5% of the DNA in some cyanobacteria. It is now reported that HIP1 is polyphyletic, occurring in several distinct cyanobacterial lineages and not defining a clade. HIP1 does not introduce gaps into sequence alignments. It aligns with partial HIP1 sites in related sequences showing that it propagates by nucleotide substitutions rather than insertion. Constructs have been created to determine the frequencies at which deletion events occur between palindromes located within the selectable marker neo. Deletion between HIP1 sites was more frequent in Synechococcus PCC 7942 than deletion between control palindromes, 5Ј-CCGATCGG-3Ј, designated PAL0. However, this is not due to a recombinase that recognises HIP1 and is peculiar to cyanobacteria because similar deletion frequencies were detected in Escherichia coli. Furthermore, the frequency of deletion of DNA flanked asymmetrically by one HIP1 site and one PAL0 site was less than the frequency of deletion of DNA flanked symmetrically by identical copies of either palindrome. This is consistent with deletion by copy-choice.

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“…Alternative models propose that various types of repetitive sequence elements may serve as substrates for intra-or intermolecular recombination (2,4). Neither model is satisfactory; slipped mispairing is inconsistent with deletions greater than Ϸ500 bp and deletions manifesting Ͻ4-bp homologies (5)(6)(7)(8)(9), whereas the recombination model does not provide a rationale for the initiation of the process.…”

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confidence: 99%

Breakpoints of gross deletions coincide with non-B DNA conformations

Bacolla

Jaworski

Larson

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

183

181

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Genomic rearrangements are a frequent source of instability, but the mechanisms involved are poorly understood. A 2.5-kbp poly(purine⅐pyrimidine) sequence from the human PKD1 gene, known to form non-B DNA structures, induced long deletions and other instabilities in plasmids that were mediated by mismatch repair and, in some cases, transcription. The breakpoints occurred at predicted non-B DNA structures. Distance measurements also indicated a significant proximity of alternating purine-pyrimidine and oligo(purine⅐pyrimidine) tracts to breakpoint junctions in 222 gross deletions and translocations, respectively, involved in human diseases. In 11 deletions analyzed, breakpoints were explicable by non-B DNA structure formation. We conclude that alternative DNA conformations trigger genomic rearrangements through recombination-repair activities. G ross chromosomal rearrangements are a common source of genetic instability (1). Thus, characterization of the underlying molecular mechanisms of mutagenesis is fundamental for our understanding of human disease. A hallmark of gross deletions is the presence of short homologous tracts (typically 2-8 bp) at the breakpoints (2), a finding that has prompted speculation as to the two distinct mechanisms postulated to be responsible for their formation. The slipped mispairing model (3) envisages that during lagging strand DNA synthesis, distantly located repeats are brought into close proximity by the looping out of the single-stranded region, thereby enabling the replication complex to ''jump'' from the proximal to the distal repeat and hence bypass the looped structure. Alternative models propose that various types of repetitive sequence elements may serve as substrates for intra-or intermolecular recombination (2, 4). Neither model is satisfactory; slipped mispairing is inconsistent with deletions greater than Ϸ500 bp and deletions manifesting Ͻ4-bp homologies (5-9), whereas the recombination model does not provide a rationale for the initiation of the process.Specific sequence motifs such as direct and inverted repeats, (RY⅐RY) n and (R⅐Y) n , in which R represents purine and Y represents pyrimidine, and four closely spaced G-rich direct repeats [i.e., (G⅐C) 3 ] undergo structural transitions from the orthodox right-handed B-helical duplex to higher energy state non-B structures (slipped hairpin͞loops, cruciforms, left-handed Z-helices, triplexes, and tetraplexes, respectively) (10-12) under torsional stress (negative supercoiling) in vivo.Early articles in bacteria and hamster cells reported isolated cases in which deletions could occur by a recombination-repair reaction mediated by cruciform structures forming at each breakpoint (13,14). Recently, the breakpoint junctions of the human constitutional translocations t(1;22), t(4;22), t(11;22), and t(17;22), which involve a common locus on chromosome 22q11.2, were found to coincide with large (Ͼ95 bp) cruciform structures (15-18), suggesting that this conformation may predispose specific loci to genomic rearrangements.The po...

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Frequency of deletion formation decreases exponentially with distance between short direct repeats

Cited by 72 publications

References 56 publications

Instability of repetitive DNA sequences: The role of replication in multiple mechanisms

Instability of repetitive DNA sequences: The role of replication in multiple mechanisms

HIP1 propagates in cyanobacterial DNA via nucleotide substitutions but promotes excision at similar frequencies in Escherichia coli and Synechococcus PCC 7942

Breakpoints of gross deletions coincide with non-B DNA conformations

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