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Bioscience Reports Aug 2017In this summary, we focus on fundamental biology of Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR)-Cas (CRISPR-associated proteins) adaptive...
In this summary, we focus on fundamental biology of Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR)-Cas (CRISPR-associated proteins) adaptive immunity in bacteria. Emphasis is placed on emerging information about functional interplay between Cas proteins and proteins that remodel DNA during homologous recombination (HR), DNA replication or DNA repair. We highlight how replication forks may act as 'trigger points' for CRISPR adaptation events, and the potential for cascade-interference complexes to act as precise roadblocks in DNA replication by an invader MGE (mobile genetic element), without the need for DNA double-strand breaks.
Topics: Bacteria; CRISPR-Cas Systems; DNA Repair; DNA Replication; DNA, Bacterial; Homologous Recombination
PubMed: 28674106
DOI: 10.1042/BSR20160297 -
Advances in Experimental Medicine and... 2017The replication of the genome of a eukaryotic cell is a complex process requiring the ordered assembly of multiprotein replisomes at many chromosomal sites. The process... (Review)
Review
The replication of the genome of a eukaryotic cell is a complex process requiring the ordered assembly of multiprotein replisomes at many chromosomal sites. The process is strictly controlled during the cell cycle to ensure the complete and faithful transmission of genetic information to progeny cells. Our current understanding of the mechanisms of eukaryotic DNA replication has evolved over a period of more than 30 years through the efforts of many investigators. The aim of this perspective is to provide a brief history of the major advances during this period.
Topics: Animals; Biology; DNA Replication; Eukaryotic Cells; History, 20th Century; History, 21st Century; Humans; Models, Theoretical; Simian virus 40; Viruses
PubMed: 29357051
DOI: 10.1007/978-981-10-6955-0_1 -
Mutation Research. Reviews in Mutation... 2021DNA replication stress is a major source of DNA damage, including double-stranded breaks that promote DNA damage response (DDR) signaling. Inefficient repair of such... (Review)
Review
DNA replication stress is a major source of DNA damage, including double-stranded breaks that promote DNA damage response (DDR) signaling. Inefficient repair of such lesions can affect genome integrity. During DNA replication different factors act on chromatin remodeling in a coordinated way. While recent studies have highlighted individual molecular mechanisms of interaction, less is known about the orchestration of chromatin changes under replication stress. In this review we attempt to explore the complex relationship between DNA replication stress, DDR and genome integrity in mammalian cells, taking into account the role of chromatin disposition as an important modulator of DNA repair. Recent data on chromatin restoration and epigenetic re-establishment after DNA replication stress are reviewed.
Topics: Animals; Chromatin; Chromatin Assembly and Disassembly; DNA Damage; DNA Replication; Genomic Instability; Humans
PubMed: 34083038
DOI: 10.1016/j.mrrev.2020.108346 -
Trends in Genetics : TIG Nov 2016DNA replication perturbs the dosage balance between genes that replicate early during S phase and those that replicate late. If propagated to influence protein content,... (Review)
Review
DNA replication perturbs the dosage balance between genes that replicate early during S phase and those that replicate late. If propagated to influence protein content, this dosage imbalance could influence cellular functions. In bacteria, mechanisms have evolved to use this imbalance to tune certain processes with the rate of cell growth. By contrast, eukaryotes buffer this dosage imbalance to ensure gene expression homeostasis also during S phase. Here, we outline classical and more recent studies describing how different organisms deal with this replication-dependent dosage imbalance, and describe recent results linking the eukaryotic buffering mechanism to replication-dependent histone acetylation. Finally, we discuss the possible implications of this buffering mechanism and speculate why it is specific to eukaryote cells.
Topics: Acetylation; Bacteria; Cell Cycle; DNA Replication; Eukaryota; Gene Dosage; Histones; S Phase; Transcription, Genetic
PubMed: 27575299
DOI: 10.1016/j.tig.2016.08.006 -
Trends in Microbiology Mar 2018Chromosomal DNA replication starts at a specific region called an origin of replication. Until recently, all organisms were thought to require origins to replicate their... (Review)
Review
Chromosomal DNA replication starts at a specific region called an origin of replication. Until recently, all organisms were thought to require origins to replicate their chromosomes. It was recently discovered that some archaeal species do not utilize origins of replication under laboratory growth conditions.
Topics: Archaea; Archaeal Proteins; Chromosomes, Archaeal; DNA Replication; DNA, Archaeal; Genes, Archaeal; Microbial Viability; Replication Origin
PubMed: 29268981
DOI: 10.1016/j.tim.2017.12.001 -
Biochimie Nov 2015Understanding how frequently spontaneous replication arrests occur and how archaea deal with these arrests are very interesting and challenging research topics. Here we... (Review)
Review
Understanding how frequently spontaneous replication arrests occur and how archaea deal with these arrests are very interesting and challenging research topics. Here we will described how genetic and imaging studies have revealed the central role of the archaeal helicase/nuclease Hef belonging to the XPF/MUS81/FANCM family of endonucleases in repair of arrested replication forks. Special focus will be on description of a recently developed combination of genetic and imaging tools to study the dynamic localization of a functional Hef::GFP (Green Fluorescent Protein) fusion protein in the living cells of halophilic archaea Haloferax volcanii. As Archaea provide an excellent and unique model for understanding how DNA replication is regulated to allow replication of a circular DNA molecule either from single or multiple replication origins, we will also summarize recent studies that have revealed peculiar features regarding DNA replication, particularly in halophilic archaea. We strongly believe that fundamental knowledge of our on-going studies will shed light on the evolutionary history of the DNA replication machinery and will help to establish general rules concerning replication restart and the key role of recombination proteins not only in bacteria, yeast and higher eukaryotes but also in archaea.
Topics: DNA Helicases; DNA Replication; Haloferax volcanii
PubMed: 26215377
DOI: 10.1016/j.biochi.2015.07.022 -
Nature Reviews. Drug Discovery Jun 2015DNA replication in cancer cells is accompanied by stalling and collapse of the replication fork and signalling in response to DNA damage and/or premature mitosis; these... (Review)
Review
DNA replication in cancer cells is accompanied by stalling and collapse of the replication fork and signalling in response to DNA damage and/or premature mitosis; these processes are collectively known as 'replicative stress'. Progress is being made to increase our understanding of the mechanisms that govern replicative stress, thus providing ample opportunities to enhance replicative stress for therapeutic purposes. Rather than trying to halt cell cycle progression, cancer therapeutics could aim to increase replicative stress by further loosening the checkpoints that remain available to cancer cells and ultimately inducing the catastrophic failure of proliferative machineries. In this Review, we outline current and future approaches to achieve this, emphasizing the combination of conventional chemotherapy with targeted approaches.
Topics: Animals; Antineoplastic Agents; Cell Cycle Checkpoints; DNA Damage; DNA Replication; Drug Delivery Systems; Humans; Neoplasms; Treatment Outcome
PubMed: 25953507
DOI: 10.1038/nrd4553 -
Current Opinion in Structural Biology Dec 2023In eukaryotic cells, genome duplication is temporally organised according to a program referred to as the replication-timing (RT) program. The RT of individual genomic... (Review)
Review
In eukaryotic cells, genome duplication is temporally organised according to a program referred to as the replication-timing (RT) program. The RT of individual genomic domains strikingly parallels the three-dimensional architecture of their chromatin contacts and subnuclear distribution. However, it is unclear whether this correspondence is coincidental or whether it indicates a causal and regulatory relationship. In either case, the nature of the molecular mechanisms ensuring this spatio-temporal coordination is still unknown. Here, we review recent evidence that begins to uncover the existence of a shared molecular machinery at the core of the spatio-temporal co-regulation of DNA replication and genome architecture. Finally, we discuss the outstanding, key question of the biological role of their coordination.
Topics: DNA Replication Timing; Chromatin; DNA Replication; Eukaryotic Cells; Genome
PubMed: 37741142
DOI: 10.1016/j.sbi.2023.102704 -
Comptes Rendus Biologies Sep 2023Replication stress is an alteration in the progression of replication forks caused by a variety of events of endogenous or exogenous origin. In precancerous lesions,... (Review)
Review
Replication stress is an alteration in the progression of replication forks caused by a variety of events of endogenous or exogenous origin. In precancerous lesions, this stress is exacerbated by the deregulation of oncogenic pathways, which notably disrupts the coordination between replication and transcription, and leads to genetic instability and cancer development. It is now well established that transcription can interfere with genome replication in different ways, such as head-on collisions between polymerases, accumulation of positive DNA supercoils or formation of R-loops. These structures form during transcription when nascent RNA reanneals with DNA behind the RNA polymerase, forming a stable DNA:RNA hybrid. In this review, we discuss how these different cotranscriptional processes disrupt the progression of replication forks and how they contribute to genetic instability in cancer cells.
Topics: Transcription, Genetic; R-Loop Structures; DNA Replication; DNA; Oncogenes; RNA; Neoplasms
PubMed: 37779381
DOI: 10.5802/crbiol.123 -
The EMBO Journal Nov 2018The DNA replication checkpoint (DRC) and the DNA damage checkpoint (DDC) are two closely linked signaling cascades that adjust S phase to the presence of DNA lesions and... (Review)
Review
The DNA replication checkpoint (DRC) and the DNA damage checkpoint (DDC) are two closely linked signaling cascades that adjust S phase to the presence of DNA lesions and other replication impediments. Two recent studies published in shed new light on their relationship in budding yeast, collectively showing that the two pathways—while sharing several factors—differ in the location and kinetics of their activation, suggesting that they constitute different branches of an integrated cellular response to impaired DNA replication.
Topics: DNA Damage; DNA Replication; DNA, Fungal; S Phase; Saccharomyces cerevisiae
PubMed: 30287420
DOI: 10.15252/embj.2018100681