Genome-wide analysis of the replication program in mammals

Farkash-Amar, Shlomit; Simon, Itamar

doi:10.1007/s10577-009-9091-5

Cited by 56 publications

(63 citation statements)

References 53 publications

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“…However, until recently, this assumption was based solely on the established general correlation between early replication timing and the transcriptional activity of gene loci in higher eukaryotes (Goren and Cedar, 2003), which, as is well known, does not apply to all transcribed loci (Taljanidisz et al, 1989;Farkash-Amar and Simon, 2010). Recent work with mouse cells in the Grummt lab produced the first experimental evidence in support of this speculation (Li et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

DNA replication initiation patterns and spatial dynamics of the human ribosomal RNA gene loci

Dimitrova

2011

Journal of Cell Science

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SummaryTypically, only a fraction of the ≥600 ribosomal RNA (rRNA) gene copies in human cells are transcriptionally active. Expressed rRNA genes coalesce in specialized nuclear compartments -the nucleoli -and are believed to replicate during the first half of S phase. Paradoxically, attempts to visualize replicating rDNA during early S phase have failed. Here, I show that, in human (HeLa) cells, earlyreplicating rDNA is detectable at the nucleolar periphery and, more rarely, even outside nucleoli. Early-replicated rDNA relocates to the nucleolar interior and reassociates with the transcription factor UBF, implying that it predominantly represents expressed rDNA units. Contrary to the established model for active gene loci, replication initiates randomly throughout the early-replicating rDNA. By contrast, mostly silent rDNA copies replicate inside the nucleoli during mid and late S phase. At this stage, replication origins are fired preferentially within the non-transcribed intergenic spacers (NTSs), and ongoing rDNA transcription is required to maintain this specific initiation pattern. I propose that the unexpected spatial dynamics of the early-replicating rDNA repeats serve to ensure streamlined efficient replication of the most heavily transcribed genomic loci while simultaneously reducing the risk of chromosome breaks and rDNA hyper-recombination.

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Section: Discussionmentioning

confidence: 99%

DNA replication initiation patterns and spatial dynamics of the human ribosomal RNA gene loci

Dimitrova

2011

Journal of Cell Science

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“…It is commonly accepted that replication of the genome is asynchronous. Open chromatin domains, often actively expressed portions of the genome, replicate earlier than heterochromatic and silent regions [26]. At the molecular level, both networks share common genomic targets, origins of replication often being present in promoter regions or transcriptional regulatory elements such as enhancers [27,28].…”

Section: Doi 101002/bies201000048mentioning

confidence: 99%

Control of DNA replication: A new facet of Hox proteins?

Miotto¹,

Graba²

2010

BioEssays

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Hox proteins are well-known as developmental transcription factors controlling cell and tissue identity, but recent findings suggest that they are also part of the cell replication machinery. Hox-mediated control of transcription and replication may ensure coordinated control of cell growth and differentiation, two processes that need to be tightly and precisely coordinated to allow proper organ formation and patterning. In this review we summarize the available data linking Hox proteins to the replication machinery and discuss the developmental and pathological implications of this new facet of Hox protein function.

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“…The locations of those origins and their relative activation times during S phase are largely conserved between individual cells defining the DNA replication program [1][2][3][4]. In recent years, the DNA replication program was mapped in different organisms [5][6][7][8][9]. Early replication was found to correlate with low mutation rate [10], high gene expression, open chromatin and a reduced nucleosome abundance [2,8,11,12].…”

Section: Introductionmentioning

confidence: 99%

Checkpoint-independent scaling of the Saccharomyces cerevisiae DNA replication program

2014

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Background: In budding yeast, perturbations that prolong S phase lead to a proportionate delay in the activation times of most origins. The DNA replication checkpoint was implicated in this scaling phenotype, as an intact checkpoint was shown to be required for the delayed activation of late origins in response to hydroxyurea treatment. In support of that, scaling is lost in cells deleted of mrc1, a mediator of the replication checkpoint signal. Mrc1p, however, also plays a role in normal replication. Results: To examine whether the replication checkpoint is required for scaling the replication profile with S phase duration we measured the genome-wide replication profile of different MRC1 alleles that separate its checkpoint function from its role in normal replication, and further analyzed the replication profiles of S phase mutants that are checkpoint deficient. We found that the checkpoint is not required for scaling; rather the unique replication phenotype of mrc1 deleted cells is attributed to the role of Mrc1 in normal replication. This is further supported by the replication profiles of tof1Δ which functions together with Mrc1p in normal replication, and by the distinct replication profiles of specific POL2 alleles which differ in their interaction with Mrc1p.

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Genome-wide analysis of the replication program in mammals

Cited by 56 publications

References 53 publications

DNA replication initiation patterns and spatial dynamics of the human ribosomal RNA gene loci

DNA replication initiation patterns and spatial dynamics of the human ribosomal RNA gene loci

Control of DNA replication: A new facet of Hox proteins?

Checkpoint-independent scaling of the Saccharomyces cerevisiae DNA replication program

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