Alternating purine-pyrimidine tracts may promote chromosomal translocations seen in a variety of human lymphoid tumours.

Boehm, Thomas; Mengle-Gaw, L.; Kees, Ursula R.; Spurr, Nigel K.; Lavenir, Isabelle; Förster, A.; Rabbitts, Terence H.

doi:10.1002/j.1460-2075.1989.tb08402.x

Cited by 152 publications

(102 citation statements)

References 60 publications

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“…It is noteworthy that mtDNA insertion has also been detected in the coding sequence of the c-myc oncogene in HeLa cells, providing a potential mechanism for tumorigenesis (Shay and Werbin 1992). Similarly, the capture of microsatellite DNA at mammalian DSBs not only has been reported experimentally (Liang et al 1998;Lin and Waldman 2001a) but also was detected at the breakpoints of lymphoid tumor-specific translocations (Boehm et al 1989). Insertion of microsatellite DNA at DSBs provides a source of genomic instability as DNA repeats are prone to expansions/contractions during cellular processes like DNA replication or DSB-induced gene conversion (Richards and Sutherland 1997;Richard et al 1999).…”

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confidence: 87%

Capture of Extranuclear DNA at Fission Yeast Double-Strand Breaks

Decottignies

2005

Genetics

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Proper repair of DNA double-strand breaks (DSBs) is necessary for the maintenance of genomic integrity. Here, a new simple assay was used to study extrachromosomal DSB repair in Schizosaccharomyces pombe. Strikingly, DSB repair was associated with the capture of fission yeast mitochondrial DNA (mtDNA) at high frequency. Capture of mtDNA fragments required the Lig4p/Pku70p nonhomologous end-joining (NHEJ) machinery and its frequency was highly increased in fission yeast cells grown to stationary phase. The fission yeast Mre11 complex Rad32p/Rad50p/Nbs1p was also required for efficient capture of mtDNA at DSBs, supporting a role for the complex in promoting intermolecular ligation. Competition assays further revealed that microsatellite DNA from higher eukaryotes was preferentially captured at yeast DSBs. Finally, cotransformation experiments indicated that, in NHEJ-deficient cells, capture of extranuclear DNA at DSBs was observed if homologies-as short as 8 bp-were present between DNA substrate and DSB ends. Hence, whether driven by NHEJ, microhomology-mediated end-joining, or homologous recombination, DNA capture associated with DSB repair is a mutagenic process threatening genomic stability.

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confidence: 87%

Capture of Extranuclear DNA at Fission Yeast Double-Strand Breaks

Decottignies

2005

Genetics

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“…We designated this region the central conserved domain. Each family had a different 3Ј tail, downstream from the central conserved domain, with potentially recombinogenic (TG) n tracts (Boehm et al 1989;Wahls et al 1990) between the central conserved domain and the 3Ј tail region. The extent of identity between the various SINE families ranged from 86% to 93% in the central conserved domain of 83 bp (nt 107-nt 189 in Fig.…”

Section: Characterization Of V-sinesmentioning

confidence: 99%

V-SINEs: A New Superfamily of Vertebrate SINEs That Are Widespread in Vertebrate Genomes and Retain a Strongly Conserved Segment within Each Repetitive Unit

Ogiwara

Miya²,

Ohshima³

et al. 2002

Genome Res.

103

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We have identified a new superfamily of vertebrate short interspersed repetitive elements (SINEs), designated V-SINEs, that are widespread in fishes and frogs. Each V-SINE includes a central conserved domain preceded by a 5Ј-end tRNA-related region and followed by a potentially recombinogenic (TG) n tract, with a 3Ј tail derived from the 3Ј untranslated region (UTR) of the corresponding partner long interspersed repetitive element (LINE) that encodes a functional reverse transcriptase. The central domain is strongly conserved and is even found in SINEs in the lamprey genome, suggesting that V-SINEs might be ∼550 Myr old or older in view of the timing of divergence of the lamprey lineage from the bony fish lineage. The central conserved domain might have been subject to some form of positive selection. Although the contemporary 3Ј tails of V-SINEs differ from one another, it is possible that the original 3Ј tail might have been replaced, via recombination, by the 3Ј tails of more active partner LINEs, thereby retaining retropositional activity and the ability to survive for long periods on the evolutionary time scale. It seems plausible that V-SINEs may have some function(s) that have been maintained by the coevolution of SINEs and LINEs during the evolution of vertebrates.[The sequences reported in this paper have been deposited in the DDBJ/GenBank database under accession nos. AB072981-AB073004. Supplemental figures are available online at http://www.genome.org.]Retroposons are genetic elements that have moved within and among genomes via an RNA intermediate (Weiner et al. 1986). They include SINEs, LINEs, LTR-retrotransposons, and retroviruses. L1 and Alu are representative of the LINEs and SINEs, respectively, in the human genome (Weiner et al. 1986;Eickbush 1994;Smit 1996). An analysis of the entire human genome revealed that retroposons constitute up to 40% of the genome and that protein-coding sequences account for only about 1.5% (International Human Genome Sequencing Consortium 2001). The above mentioned 40% of the human genome includes several clearly discernible groups of retroposons, such as L1, LINE2, Alu, and MIR, and these easily recognizable sequences represent the results of relatively recent amplifications over the past 200 Myr (International Human Genome Sequencing Consortium 2001). Accordingly, the proportion of the genome that originated from retroposons may increase up to as much as 60% to 70%, if we could identify and include ancient retroposons, which might have been amplified in the very distant past, are now barely recognizable as such, and are buried in the genome as debris. Such a putative extensive contribution of retroposons to the construction of the contemporary human genome has not been anticipated.Typical SINEs vary from 100 to 500 bp in length. They have an internal RNA polymerase III (pol III) promoter but no open reading frames (Okada 1991;Schmid and Maraia 1992;Deininger and Batzer 1993;Okada and Ohshima 1995;Schmid 1998). Many families of SINEs have been identified in multic...

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“…A recent search has revealed a non-random distribution of potential Z-forming sequences in human genes with a strong tendency to be located at transcription initiation sites in the gene (31). Furthermore, alternating purine-pyrimidine sequences have been described as being adjacent to the translocation breakpoints observed in lymphoid tumours (32) and found to be hot spot for recombination (33). Since sequences capable of forming the Z-DNA conformation exist in vivo, our results may be relevant in the processes of mutagenesis and chemical carcinogenesis especially in view of the possibility that adducts in non-B DNA may be poorly repaired (34; 35; 36).…”

Section: Resultsmentioning

confidence: 66%

The ultimate carcinogen of 4-nitroquinoline 1-oxide does not react with Z-DNA and hyperreacts with B-Z junctions

Rodolfo

Lanza

Tornaletti³

et al. 1994

Nucl Acids Res

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DNA secondary and tertiary structures are known to affect the reaction between the double helix and several damaging agents. We have previously shown that the tertiary structure of DNA influences the reactivity of 4-acetoxyaminoquinoline 1-oxide (Ac-4-HAQO), the ultimate carcinogen of 4-nitroquinoline 1-oxide (4-NQO), being more reactive with naturally supercoiled DNA than with relaxed DNA. The relative proportion of the three main stable adducts and of an unstable adduct, that resulted in strand scission and/or AP sites, was also affected by the degree of supercoiling of plasmid DNA. In this study we examined the influence of Z-DNA structure on the reactivity of Ac-4-HAQO by mapping the distribution of the two main Ac-4-HAQO adducts, C8-guanine and N2-guanine, along a (dCdG)16 sequence inserted at the BamHI site of pBR322 plasmid DNA. This insert adopted the left-handed Z and right-handed B structure depending on the superhelical density of the plasmid. Sites of C8-guanine adduct formation were determined by hot piperidine cleavage of Ac-4-HAQO modified DNA, while N2-guanine adducts were mapped by the arrest of the 3'-5' exonuclease activity of T4 DNA polymerase. The results showed that Ac-4-HAQO did not react with guanine residues when the (dC-dG)16 sequence was in Z conformation, while hyperreactivity at the B -Z junction was observed. These results indicate that Ac-4-HAQO can probe the polymorphism of DNA at the nucleotide level.

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Alternating purine-pyrimidine tracts may promote chromosomal translocations seen in a variety of human lymphoid tumours.

Cited by 152 publications

References 60 publications

Capture of Extranuclear DNA at Fission Yeast Double-Strand Breaks

Capture of Extranuclear DNA at Fission Yeast Double-Strand Breaks

V-SINEs: A New Superfamily of Vertebrate SINEs That Are Widespread in Vertebrate Genomes and Retain a Strongly Conserved Segment within Each Repetitive Unit

The ultimate carcinogen of 4-nitroquinoline 1-oxide does not react with Z-DNA and hyperreacts with B-Z junctions

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