scholarly journals An analysis of the regulation of DNA synthesis by cdk2, Cip1, and licensing factor.

1995 ◽  
Vol 129 (1) ◽  
pp. 1-15 ◽  
Author(s):  
H Yan ◽  
J Newport
Keyword(s):  
Dna Replication ◽  
Kinase Inhibitor ◽  
Negative Regulator ◽  
Sperm Chromatin ◽  
Early Event ◽  
Replication Process ◽  
P21 Protein ◽  
Licensing Factor ◽  
Additional Support

The activation of DNA replication appears to involve at least four steps. These include origin recognition, origin unwinding, primer synthesis, and a switching step to a continuous elongation mode. Moreover, in higher eukaryotes a number of studies have shown that much of the DNA replication which occurs is restricted to specific sites within the nuclei. It has been proposed that these replication foci are composed of a large number of origin sites which are clustered together into an aggregate. The molecular basis for this aggregation is currently not well understood. Regulation of the activation of DNA replication is a complicated process. The G1-S kinase cdk2 is a positive regulator of replication. The p21 protein is a negative regulator of replication both by inhibiting cdk2 kinase and the replication protein PCNA. Moreover, it has been proposed that origin usage is restricted to a single firing per cell cycle by a "licensing factor." Using a cell-free replication system derived from Xenopus eggs we have investigated at what step in the replication process these regulators participate. We present evidence that the clustered organization of DNA into foci is not a transient arrangement, but rather, it persists following DNA replication. We also find that foci form on both sperm chromatin and bacteriophage lambda DNA incubated in extracts depleted of cdk2 kinase. Therefore, our data support the conclusion that organization of chromatin into foci is an early event in the replication pathway preceding activation of cdk2 kinase. With respect to the role of cdk2 during activation of DNA replication we find that in cdk2-depleted extracts primer synthesis does not occur and RP-A remains tightly associated with foci. This strongly suggests that cdk2 kinase is required for activating the origin unwinding step of the replication process. Consistent with this interpretation we find that addition of rate limiting quantities of the cdk2 inhibitor p21 protein to an extract delays primer synthesis. Interestingly, in the presence of p21 primer synthesis does occur after a delay and then replication arrests. This is consistent with the published demonstration that p21 can inhibit PCNA, a protein required for replication beyond the priming step. Therefore, our results provide additional support to the proposal that the post-priming switching step is a key regulatory step in replication. With respect to the role of licensing factor during DNA replication it has recently been shown that treatment of mitotic extracts with kinase inhibitor DMAP inactivates "licensing factor."(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Electrical induction hypothesis to explain enhancer-promoter communication

2015 ◽  
Author(s):  
Valentina Agoni
Keyword(s):  
Transcription Factors ◽  
Dna Replication ◽  
Induction Hypothesis ◽  
Unsolved Problem ◽  
Specific Binding ◽  
Replication Machinery ◽  
Replication Process ◽  
Electrical Induction ◽  
Binding Sequence

The steps of the DNA replication process remains to be clarified. Transcription factors are supposed to find their specific binding-sequence driven by epigenetic modifications and GpC islands. But then how can the replication machinery be able to find the promoters of exactly the genes that the cell needs to transcribe in that moment? Here we hypothesize a role of DNA conductance and electrical induction to give an explanation to this unsolved problem. Our hypothesis goes in accordance with the fact that many authors identified 3D loops in the genomes.

scholarly journals Preventing re-replication of DNA in a single cell cycle: evidence for a replication licensing factor

1993 ◽  
Vol 122 (5) ◽  
pp. 993-1002 ◽  
Author(s):  
JJ Blow
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Nuclear Envelope ◽  
Kinase Inhibitor ◽  
Chromatin Modification ◽  
Replication Factor ◽  
Licensing Factor ◽  
Egg Extracts ◽  
Nuclear Envelope Assembly ◽  
Xenopus Egg Extracts

Xenopus egg extracts treated with the protein kinase inhibitor 6-dimethylaminopurine (6-DMAP) are unable to support the initiation of DNA replication. Nuclei assembled in 6-DMAP extracts behave as though they are in G2, and will not undergo another round of DNA replication until passage through mitosis. 6-DMAP extracts are functionally devoid of a replication factor that modifies chromatin in early G1 before nuclear envelope assembly, but which is itself incapable of crossing the nuclear envelope. This chromatin modification is capable of supporting only a single round of semiconservative replication. The behavior of this replication factor is sufficient to explain why eukaryotic DNA is replicated once and only once in each cell cycle, and conforms to the previous model of a Replication Licensing Factor. Cell cycle analysis shows that this putative Licensing Factor is inactive during metaphase, but becomes rapidly activated on exit from metaphase when it can modify chromatin before nuclear envelope assembly is complete.

scholarly journals A DAO1-Mediated Circuit Controls Auxin and Jasmonate Crosstalk Robustness during Adventitious Root Initiation in Arabidopsis

2019 ◽  
Vol 20 (18) ◽  
pp. 4428 ◽  
Author(s):  
Abdellah Lakehal ◽  
Asma Dob ◽  
Ondřej Novák ◽  
Catherine Bellini
Keyword(s):  
Adventitious Root ◽  
Adventitious Rooting ◽  
Negative Regulator ◽  
Early Event ◽  
Auxin Signaling ◽  
Loss Of Function ◽  
Genetic Components ◽  
Mechanistic Basis ◽  
Ja Signaling

Adventitious rooting is a post-embryonic developmental program governed by a multitude of endogenous and environmental cues. Auxin, along with other phytohormones, integrates and translates these cues into precise molecular signatures to provide a coherent developmental output. Auxin signaling guides every step of adventitious root (AR) development from the early event of cell reprogramming and identity transitions until emergence. We have previously shown that auxin signaling controls the early events of AR initiation (ARI) by modulating the homeostasis of the negative regulator jasmonate (JA). Although considerable knowledge has been acquired about the role of auxin and JA in ARI, the genetic components acting downstream of JA signaling and the mechanistic basis controlling the interaction between these two hormones are not well understood. Here we provide evidence that COI1-dependent JA signaling controls the expression of DAO1 and its closely related paralog DAO2. In addition, we show that the dao1-1 loss of function mutant produces more ARs than the wild type, probably due to its deficiency in accumulating JA and its bioactive metabolite JA-Ile. Together, our data indicate that DAO1 controls a sensitive feedback circuit that stabilizes the auxin and JA crosstalk during ARI.

scholarly journals Electrical induction hypothesis to explain enhancer-promoter communication

2015 ◽  
Author(s):  
Valentina Agoni
Keyword(s):  
Transcription Factors ◽  
Dna Replication ◽  
Induction Hypothesis ◽  
Unsolved Problem ◽  
Specific Binding ◽  
Replication Machinery ◽  
Replication Process ◽  
Electrical Induction ◽  
Binding Sequence

The steps of the DNA replication process remains to be clarified. Transcription factors are supposed to find their specific binding-sequence driven by epigenetic modifications and GpC islands. But then how can the replication machinery be able to find the promoters of exactly the genes that the cell needs to transcribe in that moment? Here we hypothesize a role of DNA conductance and electrical induction to give an explanation to this unsolved problem. Our hypothesis goes in accordance with the fact that many authors identified 3D loops in the genomes.

Is Empathy Required for Making Moral Judgments?

2018 ◽  
Author(s):  
John Deigh
Keyword(s):  
Moral Judgment ◽  
Moral Judgments ◽  
Psychopathic Personality ◽  
Critical Examination ◽  
Psychological Profile ◽  
Main Thesis ◽  
Different Types ◽  
Additional Support

This essay is a study of the nature of moral judgment. Its main thesis is that moral judgment is a type of judgment defined by its content and not its psychological profile. The essay arrives at this thesis through a critical examination of Hume’s sentimentalism and the role of empathy in its account of moral judgment. The main objection to Hume’s account is its exclusion of people whom one can describe as making moral judgments though they have no motivation to act on them. Consideration of such people, particularly those with a psychopathic personality, argues for a distinction between different types of moral judgment in keeping with the essay’s main thesis. Additional support for the main thesis is then drawn from Piaget’s theory of moral judgment in children.

scholarly journals Interactome Analysis of KIN (Kin17) Shows New Functions of This Protein

2021 ◽  
Vol 43 (2) ◽  
pp. 767-781
Author(s):  
Vanessa Pinatto Gaspar ◽  
Anelise Cardoso Ramos ◽  
Philippe Cloutier ◽  
José Renato Pattaro Junior ◽  
Francisco Ferreira Duarte Junior ◽  
...  
Keyword(s):  
Dna Replication ◽  
Protein Interactions ◽  
Ribosome Biogenesis ◽  
Cell Metabolism ◽  
Cell Types ◽  
Protein Protein Interactions ◽  
Cellular Mechanisms ◽  
Cancerous Cell ◽  
First Time

KIN (Kin17) protein is overexpressed in a number of cancerous cell lines, and is therefore considered a possible cancer biomarker. It is a well-conserved protein across eukaryotes and is ubiquitously expressed in all cell types studied, suggesting an important role in the maintenance of basic cellular function which is yet to be well determined. Early studies on KIN suggested that this nuclear protein plays a role in cellular mechanisms such as DNA replication and/or repair; however, its association with chromatin depends on its methylation state. In order to provide a better understanding of the cellular role of this protein, we investigated its interactome by proximity-dependent biotin identification coupled to mass spectrometry (BioID-MS), used for identification of protein–protein interactions. Our analyses detected interaction with a novel set of proteins and reinforced previous observations linking KIN to factors involved in RNA processing, notably pre-mRNA splicing and ribosome biogenesis. However, little evidence supports that this protein is directly coupled to DNA replication and/or repair processes, as previously suggested. Furthermore, a novel interaction was observed with PRMT7 (protein arginine methyltransferase 7) and we demonstrated that KIN is modified by this enzyme. This interactome analysis indicates that KIN is associated with several cell metabolism functions, and shows for the first time an association with ribosome biogenesis, suggesting that KIN is likely a moonlight protein.

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