Telomeric repeats on small polydisperse circular DNA (spcDNA) and genomic instability

Regev, Aviv; Cohen, Sarit; Cohen, Esther Ganelin; Bar‐Am, Irit; Lavi, Sara

doi:10.1038/sj.onc.1202250

Cited by 63 publications

(70 citation statements)

References 18 publications

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“…Recently, we have demonstrated that the minicircles replicate via a rolling-circle mechanism which generates tandem arrays of the telomeric sequence that may recombine with linear molecules of mtDNA to lengthen the telomeres (L. Tomaska, A. M. Makhov, J. D. Griffith & J. Nosek, unpublished). This may parallel alternative mechanisms of nuclear telomere maintenance involving telomeric small polydisperse circular DNAs detected in several telomerasenegative tumour cell lines (Regev et al, 1998) and Xenopus oocytes (Cohen & Mechali, 2002), or an elongation of telomeres by recombination with DNA circles as demonstrated in the yeast Kluyveromyces lactis (Natarajan & McEachern, 2002).…”

Section: Evolutionary Implicationsmentioning

confidence: 99%

Linear versus circular mitochondrial genomes: intraspecies variability of mitochondrial genome architecture in Candida parapsilosis

et al. 2004

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The yeast species Candida parapsilosis, an opportunistic pathogen, exhibits genetic and genomic heterogeneity. To assess the polymorphism at the level of mitochondrial DNA (mtDNA), the organization of the mitochondrial genome in strains belonging to the three variant groups of this species was investigated. Although these analyses revealed a group-specific restriction fragment pattern of mtDNA, strains belonging to different groups appear to have similar genes in the same gene order. An extensive survey of C. parapsilosis isolates uncovered surprising alterations in the molecular architecture of their mitochondrial genome. A screening strategy for strains harbouring mtDNA with rearranged architecture showed that nearly all strains from groups I and III possess linear mtDNA molecules terminating with arrays of tandem repeat units, while most of the group II strains have a circular mitochondrial genome. In addition, it was found that linear genophores in mitochondria of strains from different groups differ in the sequence of the mitochondrial telomeric repeat unit. The occurrence of altered forms of mtDNA among C. parapsilosis strains opens up the unique possibility to address questions concerning the evolutionary origin and replication strategy of linear and circular genomes in mitochondria.

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Section: Evolutionary Implicationsmentioning

confidence: 99%

Linear versus circular mitochondrial genomes: intraspecies variability of mitochondrial genome architecture in Candida parapsilosis

et al. 2004

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“…In Candida parapsilosis and other yeast species with linear mitochondrial DNA, rolling circles may be used for maintaining the mitochrondrial DNA termini (Tomaska et al, 2000). 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).…”

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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“…Taken together, the results suggest that the APBs contain DNA structures recognized by DNA damage checkpoint proteins, and a fraction of them induce the localization of ␥-H2AX. (41)(42)(43). Therefore, it is important to know if telomeric DNAs at APBs detected by FISH and TRF1-staining are derived from native telomeres or extrachromosomal telomeric DNAs.…”

Section: Table I Percentages Of Cells With Hrad9 Nuclear Foci And/or mentioning

confidence: 99%

Localization of hRad9, hHus1, hRad1, and hRad17 and Caffeine-sensitive DNA Replication at the Alternative Lengthening of Telomeres-associated Promyelocytic Leukemia Body

Nabetani

Yokoyama

Ishikawa

2004

Journal of Biological Chemistry

100

101

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Telomere maintenance is essential for continued cell proliferation. Although most cells accomplish this by activating telomerase, a subset of immortalized tumors and cell lines do so in a telomerase-independent manner, a process called alternative lengthening of telomeres (ALT). DNA recombination has been shown to be involved in ALT, but the precise mechanisms remain unknown. A fraction of cells in a given ALT population contain a unique nuclear structure called APB (ALTassociated promyelocytic leukemia (PML) body), which is characterized by the presence of telomeric DNA in the PML body. Here we describe that hRad9, hHus1, and hRad1, which form a DNA clamp complex that is associated with DNA damage, as well as its clamp loader, hRad17, are constitutive components of APB. Phosphorylated histone H2AX (␥-H2AX), a molecular marker of double-strand breaks (DSBs), also colocalizes with some APBs. The results suggest that telomeric DNAs at APBs are recognized as DSBs. PML staining and fluorescence in situ hybridization analyses of mitotic ALT cells revealed that telomeric DNAs present at APBs are of both extrachromosomal and native telomere origins. Furthermore, we demonstrated that DNA synthesis occurs at APBs and is significantly inhibited by caffeine, an inhibitor of phosphatidylinositol 3-kinase-related kinases. Taken together, we suggest that telomeric DNAs at APBs are recognized and processed as DSBs, leading to telomeric DNA synthesis and thereby contributing to telomere maintenance in ALT cells.

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Telomeric repeats on small polydisperse circular DNA (spcDNA) and genomic instability

Cited by 63 publications

References 18 publications

Linear versus circular mitochondrial genomes: intraspecies variability of mitochondrial genome architecture in Candida parapsilosis

Linear versus circular mitochondrial genomes: intraspecies variability of mitochondrial genome architecture in Candida parapsilosis

Alternative lengthening of telomeres in mammalian cells

Localization of hRad9, hHus1, hRad1, and hRad17 and Caffeine-sensitive DNA Replication at the Alternative Lengthening of Telomeres-associated Promyelocytic Leukemia Body

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