Small polydispersed circular DNA (spcDNA) in human cells: association with genomic instability

Cohen, Sarit; Regev, Avital; Lavi, Sara

doi:10.1038/sj.onc.1200917

Cited by 104 publications

(112 citation statements)

References 28 publications

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“…Small polydispersed circular DNA (spcDNA) was suggested to be associated with genetically unstable cells (Cohen et al, 1997). Boldog et al (1997) reported sequences with signi®cant similarity to spcDNA in a 600 bp region at the centromeric end of the 110 Kb of FRA3B sequences that they generated (GenBank Accession Number U66722).…”

Section: Discussionmentioning

confidence: 99%

Frequent homozygous deletions in the FRA3B region in tumor cell lines still leave the FHIT exons intact

et al. 1998

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FRA3B at human chromosomal band 3p14.2 is the most active common fragile site in the human genome. The molecular mechanism of fragility at this region remains unknown but does not involve expansion of a trinucleotide or minisatellite repeat as has been observed for several of the cloned rare fragile sites. Deletions and rearrangements at FRA3B have been observed in a number of distinct tumors. The recently identi®ed putative tumor suppressor gene FHIT spans FRA3B, and various groups have reported identifying deletions in this gene in dierent tumors. Using a high density of PCR ampli®able markers within FRA3B searching for deletions in the FRA3B region, we have analysed 21 tumor cell lines derived from renal cell, pancreatic, and ovarian carcinomas. We found a commonly deleted region in the renal cell and ovarian carcinoma cell lines located in the middle of an HPV16 viral integration site. Despite the presence of deletions in the FRA3B region in most of the cell lines, we did not detect alterations in FHIT exons in any of the cell lines examined. Thus, deletions of 3p14.2 in these carcinoma cell lines may simply re¯ect instability of the FRA3B region during tumor progression.

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Section: Discussionmentioning

confidence: 99%

Frequent homozygous deletions in the FRA3B region in tumor cell lines still leave the FHIT exons intact

et al. 1998

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“…Telomere repeat circles have been found in human tumors and in a human immortal cell line (Regev et al, 1998). Other types of small circular DNA have been found in human cells and are considered to be either a marker or an enhancer of genomic instability (Cohen et al, 1997;Wahl, 1989). In yeast sgs1 mutations increase the formation of rDNA circles and possibly subtelomeric repeat circles (Sinclair and Guarente, 1997).…”

Section: Rolling Circlementioning

confidence: 99%

Alternative lengthening of telomeres in mammalian cells

et al. 2002

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Some immortalized mammalian cell lines and tumors maintain or increase the overall length of their telomeres in the absence of telomerase activity by one or more mechanisms referred to as alternative lengthening of telomeres (ALT). Characteristics of human ALT cells include great heterogeneity of telomere size (ranging from undetectable to abnormally long) within individual cells, and ALT-associated PML bodies (APBs) that contain extrachromosomal telomeric DNA, telomere-speci®c binding proteins, and proteins involved in DNA recombination and replication. Activation of ALT during immortalization involves recessive mutations in genes that are as yet unidenti®ed. Repressors of ALT activity are present in normal cells and some telomerase-positive cells. Telomere length dynamics in ALT cells suggest a recombinational mechanism. Inter-telomeric copying occurs, consistent with a mechanism in which singlestranded DNA at one telomere terminus invades another telomere and uses it as a copy template resulting in net increase in telomeric sequence. It is possible that t-loops, linear and/or circular extrachromosomal telomeric DNA, and the proteins found in APBs, may be involved in the mechanism. ALT and telomerase activity can co-exist within cultured cells, and within tumors. The existence of ALT adds some complexity to proposed uses of telomererelated parameters in cancer diagnosis and prognosis, and poses challenges for the design of anticancer therapeutics designed to inhibit telomere maintenance.

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“…spcDNAs can also be induced or increased by DNA damaging agents (Cohen and Lavi 1996;Cohen et al, 1997) and inhibitors of DNA synthesis, including the common fragile site inducer aphidicolin (Sunnerhagen et al, 1989). The presence of sequences with considerable homology to spcDNA right in the middle of two of the common fragile sites may therefore not be coincidental.…”

Section: Discussionmentioning

confidence: 99%

FRA7G extends over a broad region: coincidence of human endogenous retroviral sequences (HERV-H) and small polydispersed circular DNAs (spcDNA) and fragile sites

Huang

Qian

Proffit³

et al. 1998

Oncogene

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FRA7G is an aphidicolin-inducible common fragile site at human chromosomal band 7q31.2. This region is frequently altered in a number of dierent tumor types including prostate, breast, and ovarian cancer. It has also been hypothesized that this region contains an important tumor suppressor gene which is mutated during the development of these cancers or an oncogene which is ampli®ed. We previously used a FISH-based approach to isolate YAC clones which spanned FRA7G. In this report, we describe the isolation and restriction endonuclease mapping of three overlapping P1 clones which cover FRA7G and the region frequently altered in the dierent cancers. FISH-based analysis of these clones reveals that aphidicolin-induced breakage in the FRA7G region occurs over a region of at least 300 Kb in length. We have also localized a previously sequenced BAC clone to this region. The sequence obtained from this clone reveals the presence of an endogenous retroviral sequence (HERV-H) in the midst of the FRA7G region as well as sequences with homology to small polydispersed circular DNAs (spcDNAs). Thus for the ®rst two cloned common fragile sites, FRA7G and FRA3B, there is an association with both spcDNAs and hot-spots for viral integration.

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Small polydispersed circular DNA (spcDNA) in human cells: association with genomic instability

Cited by 104 publications

References 28 publications

Frequent homozygous deletions in the FRA3B region in tumor cell lines still leave the FHIT exons intact

Frequent homozygous deletions in the FRA3B region in tumor cell lines still leave the FHIT exons intact

Alternative lengthening of telomeres in mammalian cells

FRA7G extends over a broad region: coincidence of human endogenous retroviral sequences (HERV-H) and small polydispersed circular DNAs (spcDNA) and fragile sites

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