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Regulating DNA Replication in Eukarya

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TLDR
Work from several organisms has revealed a conserved strategy whereby inactive replication complexes are assembled onto DNA during periods of low CDK and high APC activity but are competent to execute genome duplication only when these activities are reversed.
Abstract
DNA replication is tightly controlled in eukaryotic cells to ensure that an exact copy of the genetic material is inherited by both daughter cells. Oscillating waves of cyclin-dependent kinase (CDK) and anaphase-promoting complex/cyclosome (APC/C) activities provide a binary switch that permits the replication of each chromosome exactly once per cell cycle. Work from several organisms has revealed a conserved strategy whereby inactive replication complexes are assembled onto DNA during periods of low CDK and high APC activity but are competent to execute genome duplication only when these activities are reversed. Periods of high CDK and low APC/C serve an essential function by blocking reassembly of replication complexes, thereby preventing rereplication. Higher eukaryotes have evolved additional CDK-independent mechanisms for preventing rereplication.

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Citations
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Posted ContentDOI

RTEL1 and MCM10 overcome topological stress during vertebrate replication termination

TL;DR: Overall, the data identify an alternate mechanism of termination involving RTEL1 and MCM10 that can be used to complete DNA synthesis under conditions of topological stress.
Journal ArticleDOI

Neural network and kinetic modelling of human genome replication reveal replication origin locations and strengths

TL;DR: It is shown that MRT and RFD data are highly consistent with each other but contain information at different spatial frequencies, and an analytical formula is uncovered that predicts intrinsic from observed origin efficiency combined with MRT data.
Journal ArticleDOI

RTEL1 and MCM10 overcome topological stress during vertebrate replication termination

- 01 Feb 2023 - 
TL;DR: In this paper , the helicase RTEL1 and the replisome protein MCM10 are enriched on chromatin during fork convergence and are crucially important for fork convergence under conditions of topological stress.
Journal ArticleDOI

Bioinformatical dissection of fission yeast DNA replication origins

TL;DR: A model that describes how multiple functional elements specify DNA replication origins in fission yeast genome is provided to distinguish efficient replication origins from the rest of chromosome arms with high accuracy is provided.
Book ChapterDOI

Comparison of Bacterial and Eukaryotic Replisome Components

TL;DR: In this paper , the authors compare the structure and mechanisms of the central proteins that act directly at replication forks in bacteria to those of eukaryotes and compare the way these proteins organize their functions within a dynamic replisome machine.
References
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Journal ArticleDOI

Comprehensive Identification of Cell Cycle–regulated Genes of the Yeast Saccharomyces cerevisiae by Microarray Hybridization

TL;DR: A comprehensive catalog of yeast genes whose transcript levels vary periodically within the cell cycle is created, and it is found that the mRNA levels of more than half of these 800 genes respond to one or both of these cyclins.
Journal ArticleDOI

Genetic instabilities in human cancers

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Journal ArticleDOI

Cell cycle, CDKs and cancer: a changing paradigm

TL;DR: Genetic evidence suggests that tumour cells may also require specific interphase CDKs for proliferation, and selective CDK inhibition may provide therapeutic benefit against certain human neoplasias.
Journal ArticleDOI

The DNA Damage Response: Ten Years After

TL;DR: This work has witnessed an explosion in understanding of DNA damage sensing, signaling, and the complex interplay between protein phosphorylation and the ubiquitin pathway employed by the DDR network to execute the response to DNA damage.
Journal ArticleDOI

Ubiquitin ligases: cell-cycle control and cancer

TL;DR: A better understanding of the ubiquitylation machinery will provide new insights into the regulatory biology of cell-cycle transitions and the development of anti-cancer drugs.
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