Checkpoint Regulation of DNA Replication

Boye, Erik; Skjølberg, Henriette C.; Grallert, Beáta

doi:10.1007/978-1-60327-815-7_4

Cited by 12 publications

(6 citation statements)

References 92 publications

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“…The roles of biological checkpoints have been extensively characterized in cell division where the failure of these feedback controls leads to cell death or extensive proliferation (93-95). When neurons are misplaced or misconnected for genetic or environmental reasons they can signal this situation by arresting some of their developmental sequences.…”

Section: Checkpoints Signal Branch Points In Genetic Programsmentioning

confidence: 99%

Phenotypic checkpoints regulate neuronal development

Ben-Ari

Spitzer

2010

Trends in Neurosciences

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Nervous system development proceeds by sequential gene expression mediated by cascades of transcription factors in parallel with sequences of patterned network activity driven by receptors and ion channels. These sequences are cell type-and developmental stage-dependent and modulated by paracrine actions of substances released by neurons and glia. How and to what extent these sequences interact to enable neuronal network development is not understood. Recent evidence demonstrates that CNS development requires intermediate stages of differentiation providing functional feedback that influences gene expression. We suggest that embryonic neuronal functions constitute a series of phenotypic checkpoint signatures; neurons failing to express these functions are delayed or developmentally arrested. Such checkpoints are likely to be a general feature of neuronal development and may constitute presymptomatic signatures of neurological disorders when they go awry. Constructing the nervous system: the scale of the problemThe complexity of the nervous system makes the developmental assembly of this structure unusually challenging. Neuronal phenotypes are specified and synaptic connections are formed with prodigious specificity. An argument can be made that the brain begins simply and that complexity is built up gradually. However, 80% of 20,000 mouse genes are expressed in the adult nervous system (1). With 10 11 neurons making 10 15 synapses, this number of genes is insufficient to program the development of the nervous system on a single-gene-to-singlecomponent basis. How is such a complex program regulated during development? Cascades of transcription factors play an important role (2,3). However, there is significant potential for disruptions of neuronal development by mistakes in transcriptional machinery or perturbations of gene expression. Indeed there are a vast number of genetically or environmentally driven developmental disorders, with unfortunate societal and financial impacts.Fortunately, developing neurons are not mute during development. They express cell and developmental stage-specific sequences of voltage-gated and transmitter receptor-linked ion channel currents that provide read-outs of their state of differentiation Often due to the expression of different channel subunits, immature currents are more "sloppy" than adult ones and their long synaptic durations account for the relatively slow kinetics that enable calcium influx at early developmental stages (4-8). Immature networks also follow a specific © 2010 Elsevier Ltd. All rights reserved.Correspondence to: Ben-Ari, Y. (ben-ari@inmed.univ-mrs.fr) or Spitzer, N.C (nspitzer@ucsd.edu). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the produc...

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Section: Checkpoints Signal Branch Points In Genetic Programsmentioning

confidence: 99%

Phenotypic checkpoints regulate neuronal development

Ben-Ari

Spitzer

2010

Trends in Neurosciences

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“…G1/S checkpoint control is a key rate-limiting step in the cell cycle regulatory pathway. Its abnormality is closely related to the multifactorial, multistage, and multistep oncogenesis of tumor and is one of the research hotspots on the mechanism of tumor progression (Boye et al, 2009). There are many factors involved in G1/S checkpoint regulation such as cyclin-dependent kinase family (CDKs), cyclin-dependent kinase activator family (CDKIs), cyclin-dependent kinase inhibitor family (CDKNS), cyclin (Cyclin), p21, Rb, and Myc (Reed, 1997).…”

Section: Discussionmentioning

confidence: 99%

Screening and Identification of Distant Metastasis‐Related Differentially Expressed Genes in Human Squamous Cell Lung Carcinoma

Wang¹,

Zhou²,

Xiong³

et al. 2012

The Anatomical Record

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Distant metastasis is one of the leading causes of lung cancer death. Detecting the early-stage molecular alternations in primary tumors, such as gene expression differences, provides a ''prognostic'' value to the precaution of tumor metastasis. The aim of this article is to screen and identify the metastasis-related genes in human squamous cell lung carcinoma. Primary tumor tissues of nine patients with subsequent metastasis and eight patients without metastasis were selected to perform the gene microarray experiment. GO and pathway analyses were used to determine the differentially expressed genes. Two identified genes were further validated by real-time quantitative reverse transcription polymerase chain reaction (PCR) (real-time qRT-PCR). Two hundred and thirty-eight differentially expressed genes were detected in gene chip experiment, including 51 up-regulated genes and 187 down-regulated genes. These genes were involved in several cellular processes, including cell adhesion, cell cycle regulation, and apoptosis. GO analysis showed that the differentially expressed genes participated in a wide ranging of metastasis-related processes, including extracellular region and regulation of liquid surface tension. In addition, pathway analysis demonstrated that the differentially expressed genes were enriched in pathways related to cell cycle and Wnt signaling. Real-time qRT-PCR validation experiment of LCN2 and PDZK1IP1 showed a consistent up-regulation in the metastasis group. The metastasis of human squamous cell lung carcinoma is a complex process that is regulated by multiple gene alternations on the expression levels. The 238 differentially expressed genes identified in this study presumably contain a core set of genes involved in tumor metastasis. The real-time qRT-PCR results of PDZK1IP1 and LCN2 validated the reliability of this gene microarray experiment. Anat Rec,

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“…Three assays were used to discriminate between cells in G 1 and S phase in the present work: the loading of the preRC onto chromatin and the presence of Rum1 and phosphorylated Cdc2 (22). The preRC formation is essential for the initiation of DNA replication and occurs in G 1 phase.…”

Section: Resultsmentioning

confidence: 99%

Induction of a G ₁ -S checkpoint in fission yeast

Bøe

Krohn

Rødland

et al. 2012

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

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Entry into S phase is carefully regulated and, in most organisms, under the control of a G 1 -S checkpoint. We have previously described a G 1 -S checkpoint in fission yeast that delays formation of the prereplicative complex at chromosomal replication origins after exposure to UV light (UVC). This checkpoint absolutely depends on the Gcn2 kinase. Here, we explore the signal for activation of the Gcn2-dependent G 1 -S checkpoint in fission yeast. If some form of DNA damage can activate the checkpoint, deficient DNA repair should affect the length of the checkpoint-induced delay. We find that the cell-cycle delay differs in repair-deficient mutants from that in wild-type cells. However, the duration of the delay depends not only on the repair capacity of the cells, but also on the nature of the repair deficiency. First, the delay is abolished in cells that are deficient in the early steps of repair. Second, the delay is prolonged in repair mutants that fail to complete repair after the incision stage. We conclude that the G 1 -S delay depends on damage to the DNA and that the activating signal derives not from the initial DNA damage, but from a repair intermediate(s). Surprisingly, we find that activation of Gcn2 does not depend on the processing of DNA damage and that activated Gcn2 alone is not sufficient to delay entry into S phase in UVC-irradiated cells. Thus, the G 1 -S delay depends on at least two different inputs.

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Checkpoint Regulation of DNA Replication

Cited by 12 publications

References 92 publications

Phenotypic checkpoints regulate neuronal development

Phenotypic checkpoints regulate neuronal development

Screening and Identification of Distant Metastasis‐Related Differentially Expressed Genes in Human Squamous Cell Lung Carcinoma

Induction of a G ₁ -S checkpoint in fission yeast

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Checkpoint Regulation of DNA Replication

Cited by 12 publications

References 92 publications

Phenotypic checkpoints regulate neuronal development

Phenotypic checkpoints regulate neuronal development

Screening and Identification of Distant Metastasis‐Related Differentially Expressed Genes in Human Squamous Cell Lung Carcinoma

Induction of a G 1 -S checkpoint in fission yeast

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Induction of a G ₁ -S checkpoint in fission yeast