Illegitimate recombination in the histone multigenic family generates circular DNAs in Drosophila embryos

Pont, Geneviève; Degroote, Fabienne; Picard, Georges

doi:10.1093/nar/16.18.8817

Cited by 17 publications

(19 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, the increase in plasmid dimerization, also observed for the (GAA⅐TTC) n repeat associated with Friedreich ataxia (33), is consistent with the stimulation of both intra-and intermolecular recombination. Third, deleted DNA fragments (products of the deletion process) may be recovered as circular molecules (6,41). Fourth, the parental sequence is generally reconstituted from the products' ends with little, if any, nucleotide loss.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

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

View full text Add to dashboard Cite

show abstract

“…It is now documented in several instances, including the present case, that spc DNAs can arise through simple recombination between flanking direct repeats (7,21,22,26,27). Irrespective of the precise mechanism, some reproducible event must be involved in generating this particular THE-1 related circle.…”

Section: Resultsmentioning

confidence: 66%

“…It is not known whether these imperfect "patchy" repeats direct or are related to the proposed recombination event, but their presence is certainly worth noting, and suggestive of a function. Such site specific recombination between direct repeats in the histone gene cluster is known to produce extrachromosomal circular DNAs in Drosophila embryos (21). Similarly, a portion of an L-1 transposable element, along with adjacent single-copy sequences, was isolated from HeLa circular DNA (22).…”

Section: Resultsmentioning

confidence: 99%

Recombination mediates production of an extrachromosomal circular DNA containing a transposon-like human element, THE-1

Misra¹,

Matera²,

Schmid³

et al. 1989

Nucl Acids Res

View full text Add to dashboard Cite

“…We used a simple assay system in which a minus strand of a short DNA duplex is transferred onto a single-stranded circle harboring sequence complementarity by the action of RecA protein. The constructs were designed so that distal joints (20) were formed because these types of joints are considered the most stable compared with proximal or medial pairing partners. We have recently begun a comparative analysis of proximal, medial, and distal joint molecule formation under similar reaction conditions, and our preliminary findings suggest that RNA obviates this discrimination.…”

Section: Discussionmentioning

confidence: 99%

A role for RNA synthesis in homologous pairing events.

Kotani¹,

Kmiec²

1994

Mol. Cell. Biol.

View full text Add to dashboard Cite

The relationship between RNA synthesis and homologous pairing in vitro, catalyzed by RecA protein, was examined by using an established strand transfer assay system. When a short DNA duplex is mixed with single-stranded circles, RecA protein promotes the transfer of the minus strand of the duplex onto the complementary region of the plus-strand circle, with the displacement of the plus strand of the duplex.However, if minus-strand RNA is synthesized from the duplex pairing partner, joint molecules containing the RNA transcript, the plus strand of the DNA duplex, and the plus-strand circle are also observed to form. This reaction, which is dependent on RNA polymerase, sequence homology, and RecA protein, produces a joint molecule that can be dissolved by treatment with RNase H but not RNase A. Under these reaction conditions, product molecules form even when the length of shared homology between duplex and circle is reduced to 15 bp.Among the most important phases of the recombination process is the homologous alignment of DNA molecules. The formation of this structure is a requirement for progression through the exchange of genetic material based on sequence homology. Once alignment has occurred, heteroduplexed molecules are created and subsequent resolution completes the recombination cycle. Much of the information about homologous pairing has been gathered from studies on the action of the Escherichia coli RecA protein (see reviews, see references 3 and 21). This remarkable 37,842-Da protein promotes the homologous pairing of a wide variety of DNA substrates, including duplex linear DNA and single-stranded circles. This duo has been used extensively in the in vitro characterization of homologous recombination, and the results of these experiments contributed to the identification of certain stages within the genetic exchange process.One of the reaction parameters surrounding the duplex by circle pairing reaction is the length of homology shared by the two molecules. In recombination assays in which RecA protein acted as the recombinase, the lower limit of complementarity was originally defined to lie between 30 and 151 bp (6). St., Philadelphia, PA 19107. accessibility of RecA for the homologous regions within the duplex (14,15). Subsequently, we demonstrated that transcription through the chromatin template destabilizes the nucleosome, facilitating RecA-promoted joint molecule formation. During the course of our preliminary studies on DNA templates devoid of nucleosomes, we detected the RNA transcript itself in the products of the strand transfer reaction. In some of these reactions, the positive strand of the duplex molecule was transferred in conjunction with the RNA transcript, forming a complex that consisted of plus-strand linear duplex DNA, minus-strand RNA, and plus-strand DNA circle. The creation of this complex was found to be dependent on RecA protein, single-stranded circles, minus-strand RNA, and DNA homology.In this report, we focus on the length of DNA homology required to facilitate the (co...

show abstract

Illegitimate recombination in the histone multigenic family generates circular DNAs in Drosophila embryos

Cited by 17 publications

References 55 publications

Breakpoints of gross deletions coincide with non-B DNA conformations

Breakpoints of gross deletions coincide with non-B DNA conformations

Recombination mediates production of an extrachromosomal circular DNA containing a transposon-like human element, THE-1

A role for RNA synthesis in homologous pairing events.

Contact Info

Product

Resources

About