Think global, act local — how to regulate S phase from individual replication origins

Pasero, Philippe; Schwob, Étienne

doi:10.1016/s0959-437x(00)00067-8

Cited by 29 publications

(22 citation statements)

References 81 publications

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“…A contingency of an overreplication type mechanism is the presence of active origins of replication that are presumably organized in clusters in the amplified region (31). Active, closely spaced origins are essential conditions for the stable duplication of a region, and therefore deregulation of replication origin firing may drive the amplification process (32,33). We recently confirmed the presence of stalled replication forks and perturbed replication origin activation at both genomic and viral sequences within the amplicon.…”

Section: Resultssupporting

confidence: 53%

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Genomic Organization of Amplified MYC Genes Suggests Distinct Mechanisms of Amplification in Tumorigenesis

Herrick¹,

Conti²,

Teissier

et al. 2005

Cancer Research

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Integration of the human papillomavirus (HPV) genome into the host genome is associated with the disruption of the HPV E2 gene and with amplification and rearrangement of the viral and flanking cellular sequences. Molecular characterization of the genomic structures of coamplified HPV sequences and oncogenes provides essential information concerning the mechanisms of amplification and their roles in carcinogenesis. Using fluorescent hybridization on stretched DNA molecules in two cervical cancer-derived cell lines, we have elucidated the genomic structures of amplified regions containing HPV/myc genes over several hundreds of kilobases. Direct visualization of hybridization signals on individual DNA molecules suggests that overreplication and breakagefusion-bridge-type mechanisms are involved in the genomic instability associated with HPV cervical cancers. Further analysis from two other genital cancer-derived cell lines reveals a recurrent motif of amplification, probably generated by a common mechanism involving overreplication upon viral integration. Interestingly, different amplification patterns seem to be correlated with the disease outcome, thus providing new insights into HPV-related cancer development and tumor progression. (Cancer Res 2005; 65(4): 1174-9)

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Section: Resultssupporting

confidence: 53%

“…Inefficient replication of DNA resulting in unduplicated regions of the genome at mitosis may be due to abnormal replication initiation or perturbed fork progression (32). Therefore, a break-fusion-bridgetype mechanism of amplification may involve impaired DNA replication.…”

Section: Resultsmentioning

confidence: 99%

Genomic Organization of Amplified MYC Genes Suggests Distinct Mechanisms of Amplification in Tumorigenesis

Herrick¹,

Conti²,

Teissier

et al. 2005

Cancer Research

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show abstract

“…Although the activation of individual replication origins may depend on epigenetic factors (1,2), all of these autonomously replicating sequences (ARSs) allow extrachromosomal replication when inserted into plasmids (3). In the fission yeast Saccharomyces pombe, replication origins are more extended than in budding yeast, and, although they show no consensus sequence in the strict sense, they contain AT-rich elements that serve as binding sites for the origin recognition complex (4).…”

mentioning

confidence: 99%

Nuclear scaffold/matrix attached region modules linked to a transcription unit are sufficient for replication and maintenance of a mammalian episome

Jenke

Stehle

Herrmann

et al. 2004

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

150

149

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The activation of mammalian origins of replication depends so far on ill understood epigenetic events, such as binding of transcription factors, chromatin structure, and nuclear localization. Understanding these mechanisms is not only a scientific challenge but also represents a prerequisite for the rational design of nonviral episomal vectors for mammalian cells. In this paper, we demonstrate that a tetramer of a 155-bp minimal nuclear scaffold͞matrix attached region DNA module linked to an upstream transcription unit is sufficient for replication and mitotic stability of a mammalian episome in the absence of selection. Fluorescence in situ hybridization analyses, crosslinking with cis-diammineplatinum(II)-dichloride and chromatin immunoprecipitation demonstrate that this vector associates with the nuclear matrix or scaffold in vivo by means of specific interaction of the nuclear scaffold͞matrix attached region with the nuclear matrix protein SAF-A. Results presented in this paper define the minimal requirements of an episomal vector for mammalian cells on the molecular level.DNA replication ͉ mitotic stability ͉ nuclear matrix ͉ SAF-A

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“…In most cells, replication initiates at specific sequences, and distinct origins fire at different times in the S phase (2,3). We are interested in developmental transitions in origin usage and the replication timing program in Xenopus.…”

mentioning

confidence: 99%

Aphidicolin Triggers a Block to Replication Origin Firing inXenopus Egg Extracts

Marheineke¹,

Hyrien

2001

Journal of Biological Chemistry

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DNA replication origins are located at random with respect to DNA sequence in Xenopus early embryos and on DNA replicated in Xenopus egg extracts. We have recently shown that origins fire throughout the S phase in Xenopus egg extracts. To study the temporal regulation of origin firing, we have analyzed origin activation in sperm nuclei treated with the DNA polymerase inhibitor aphidicolin. Sperm chromatin was incubated in Xenopus egg extracts in the presence of aphidicolin and transferred to a fresh extract, and digoxigenin-dUTP and biotin-dUTP were added at various times after aphidicolin release to selectively label early and late replicating DNA. Molecular combing analysis of single DNA fibers showed that only a fraction of potential origins were able to initiate in the presence of aphidicolin. After release from aphidicolin, the remaining origins fired asynchronously throughout the S phase. Therefore, initiation during the S phase depends on the normal progression of replication forks assembled at earlier activated origins. Caffeine, an inhibitor of the checkpoint kinases ATR and ATM, did not relieve the aphidicolin-induced block to origin firing. We conclude that a caffeine-insensitive intra-S phase checkpoint regulates origin activation when DNA synthesis is inhibited in Xenopus egg extracts.

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Think global, act local — how to regulate S phase from individual replication origins

Cited by 29 publications

References 81 publications

Genomic Organization of Amplified MYC Genes Suggests Distinct Mechanisms of Amplification in Tumorigenesis

Genomic Organization of Amplified MYC Genes Suggests Distinct Mechanisms of Amplification in Tumorigenesis

Nuclear scaffold/matrix attached region modules linked to a transcription unit are sufficient for replication and maintenance of a mammalian episome

Aphidicolin Triggers a Block to Replication Origin Firing inXenopus Egg Extracts

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