Regulating DNA Replication in Eukarya
Reads0
Chats0
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.read more
Citations
More filters
Journal ArticleDOI
Structure of the eukaryotic MCM complex at 3.8 A
Ningning Li,Yuanliang Zhai,Yixiao Zhang,Wanqiu Li,Maojun Yang,Jianlin Lei,Bik Kwoon Tye,Ning Gao +7 more
TL;DR: Cryo-electron microscopy reports a near-atomic structure of the MCM2–7 double hexamer purified from yeast G1 chromatin that shows unusual features of the twisted and tilted single hexamers that suggest a concerted mechanism for the melting of origin DNA that requires structural deformation of the intervening DNA.
Journal ArticleDOI
The impact of replication stress on replication dynamics and DNA damage in vertebrate cells.
TL;DR: The interplay between replication stress and the S phase checkpoint is a key determinant of genome maintenance, and has a major impact on human diseases, notably, tumour initiation and progression.
Journal ArticleDOI
Single-Molecule Studies of Origin Licensing Reveal Mechanisms Ensuring Bidirectional Helicase Loading
TL;DR: In this article, the authors demonstrate that double-hexamer formation is the result of sequential loading of individual Mcm2-7 replicative helicase around DNA licenses eukaryotic origins of replication.
Journal ArticleDOI
Rif1 Controls DNA Replication Timing in Yeast through the PP1 Phosphatase Glc7
Stefano Mattarocci,Maksym Shyian,Laure Lemmens,Pascal Damay,Dogus Murat Altintas,Tianlai Shi,Clinton R. Bartholomew,Nicolas H. Thomä,Christopher F.J. Hardy,David Shore +9 more
TL;DR: Rif1 RVxF/SILK motif-dependent recruitment of Glc7 to telomeres and earlier replication of these regions in cells where the motifs are mutated are demonstrated.
Journal ArticleDOI
Mechanisms for Initiating Cellular DNA Replication
TL;DR: A review of DNA replication in bacteria, archaea, and eukaryotes can be found in this paper, with a focus on comparing and contrasting molecular mechanisms among organisms, showing that many key participants have markedly different activities and appear to have evolved convergently.
References
More filters
Journal ArticleDOI
Comprehensive Identification of Cell Cycle–regulated Genes of the Yeast Saccharomyces cerevisiae by Microarray Hybridization
Paul T. Spellman,Gavin Sherlock,Gavin Sherlock,Michael Q. Zhang,Vishwanath R. Iyer,Kirk R. Anders,Michael B. Eisen,Patrick O. Brown,Patrick O. Brown,David Botstein,Bruce Futcher +10 more
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
TL;DR: There is now evidence that most cancers may indeed be genetically unstable, but that the instability exists at two distinct levels, and recognition and comparison of these instabilities are leading to new insights into tumour pathogenesis.
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.