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Cancer Science Feb 2018DNA replication is one of the fundamental biological processes in which dysregulation can cause genome instability. This instability is one of the hallmarks of cancer... (Review)
Review
DNA replication is one of the fundamental biological processes in which dysregulation can cause genome instability. This instability is one of the hallmarks of cancer and confers genetic diversity during tumorigenesis. Numerous experimental and clinical studies have indicated that most tumors have experienced and overcome the stresses caused by the perturbation of DNA replication, which is also referred to as DNA replication stress (DRS). When we consider therapeutic approaches for tumors, it is important to exploit the differences in DRS between tumor and normal cells. In this review, we introduce the current understanding of DRS in tumors and discuss the underlying mechanism of cancer therapy from the aspect of DRS.
Topics: DNA Damage; DNA Replication; Gene Regulatory Networks; Genomic Instability; Humans; Neoplasms
PubMed: 29168596
DOI: 10.1111/cas.13455 -
Journal of Bacteriology Jul 2017In bacteria, replication forks assembled at a replication origin travel to the terminus, often a few megabases away. They may encounter obstacles that trigger replisome... (Review)
Review
In bacteria, replication forks assembled at a replication origin travel to the terminus, often a few megabases away. They may encounter obstacles that trigger replisome disassembly, rendering replication restart from abandoned forks crucial for cell viability. During the past 25 years, the genes that encode replication restart proteins have been identified and genetically characterized. In parallel, the enzymes were purified and analyzed , where they can catalyze replication initiation in a sequence-independent manner from fork-like DNA structures. This work also revealed a close link between replication and homologous recombination, as replication restart from recombination intermediates is an essential step of DNA double-strand break repair in bacteria and, conversely, arrested replication forks can be acted upon by recombination proteins and converted into various recombination substrates. In this review, we summarize this intense period of research that led to the characterization of the ubiquitous replication restart protein PriA and its partners, to the definition of several replication restart pathways , and to the description of tight links between replication and homologous recombination, responsible for the importance of replication restart in the maintenance of genome stability.
Topics: Bacteria; DNA Repair; DNA Replication; DNA, Bacterial; Mutation
PubMed: 28320884
DOI: 10.1128/JB.00102-17 -
Advances in Experimental Medicine and... 2017DNA replication ensures the accurate duplication of the genome at each cell cycle. During S phase, tens of thousands of replication origins throughout the vertebrate... (Review)
Review
DNA replication ensures the accurate duplication of the genome at each cell cycle. During S phase, tens of thousands of replication origins throughout the vertebrate genome are activated according to a spatiotemporal program. The genome-wide mapping of origins in several model systems has identified G-quadruplexes-higher-order DNA structures formed from G-rich sequences-as potential key regulators of origin activity. Here, I describe genetic experiments demonstrating the role of G-quadruplexes in origin function. I discuss the different means by which G-quadruplexes might regulate origin function. Finally, comparisons of replicon organization in the three domains of life suggest that G-quadruplexes may have retained a conserved role in origin function during evolution.
Topics: Animals; Chromosome Mapping; DNA; DNA Replication; G-Quadruplexes; Humans; Replication Origin; Vertebrates
PubMed: 29357063
DOI: 10.1007/978-981-10-6955-0_13 -
Current Opinion in Genetics &... Dec 2021Helicases are in the spotlight of DNA metabolism and are critical for DNA repair in all domains of life. At their biochemical core, they bind and hydrolyze ATP,... (Review)
Review
Helicases are in the spotlight of DNA metabolism and are critical for DNA repair in all domains of life. At their biochemical core, they bind and hydrolyze ATP, converting this energy to translocate unidirectionally, with different strand polarities and substrate binding specificities, along one strand of a nucleic acid. In doing so, DNA and RNA helicases separate duplex strands or remove nucleoprotein complexes, affecting DNA repair and the architecture of replication forks. In this review, we focus on recent advances on the roles and regulations of DNA helicases in homologous recombination repair, a critical pathway for mending damaged chromosomes and for ensuring genome integrity.
Topics: DNA Damage; DNA Helicases; DNA Repair; DNA Replication; Homologous Recombination; Recombinational DNA Repair
PubMed: 34271541
DOI: 10.1016/j.gde.2021.06.009 -
Cold Spring Harbor Perspectives in... May 2016The genome is subject to a diverse array of epigenetic modifications from DNA methylation to histone posttranslational changes. Many of these marks are somatically... (Review)
Review
The genome is subject to a diverse array of epigenetic modifications from DNA methylation to histone posttranslational changes. Many of these marks are somatically stable through cell division. This article focuses on our knowledge of the mechanisms governing the inheritance of epigenetic marks, particularly, repressive ones, when the DNA and chromatin template are duplicated in S phase. This involves the action of histone chaperones, nucleosome-remodeling enzymes, histone and DNA methylation binding proteins, and chromatin-modifying enzymes. Last, the timing of DNA replication is discussed, including the question of whether this constitutes an epigenetic mark that facilitates the propagation of epigenetic marks.
Topics: DNA Methylation; DNA Replication; Epigenesis, Genetic; Gene Expression Regulation; Histone Chaperones; Histone Code; Models, Genetic; Protein Processing, Post-Translational
PubMed: 27141050
DOI: 10.1101/cshperspect.a019372 -
Genes Apr 2023Mutations of numerous genes involved in DNA replication, DNA repair, and DNA damage response (DDR) pathways lead to a variety of human diseases, including aging and...
Mutations of numerous genes involved in DNA replication, DNA repair, and DNA damage response (DDR) pathways lead to a variety of human diseases, including aging and cancer [...].
Topics: Humans; DNA Damage; DNA Repair; Mutation; Neoplasms; DNA Replication
PubMed: 37107651
DOI: 10.3390/genes14040893 -
Annual Review of Genetics Nov 2023Transcription and replication both require large macromolecular complexes to act on a DNA template, yet these machineries cannot simultaneously act on the same DNA... (Review)
Review
Transcription and replication both require large macromolecular complexes to act on a DNA template, yet these machineries cannot simultaneously act on the same DNA sequence. Conflicts between the replication and transcription machineries (transcription-replication conflicts, or TRCs) are widespread in both prokaryotes and eukaryotes and have the capacity to both cause DNA damage and compromise complete, faithful replication of the genome. This review will highlight recent studies investigating the genomic locations of TRCs and the mechanisms by which they may be prevented, mitigated, or resolved. We address work from both model organisms and mammalian systems but predominantly focus on multicellular eukaryotes owing to the additional complexities inherent in the coordination of replication and transcription in the context of cell type-specific gene expression and higher-order chromatin organization.
Topics: Animals; Transcription, Genetic; DNA Replication; Genomic Instability; Eukaryota; DNA Damage; Mammals
PubMed: 37552891
DOI: 10.1146/annurev-genet-080320-031523 -
Aging Dec 2017
Topics: Animals; CDC2 Protein Kinase; Cell Cycle; Cell Cycle Proteins; DNA Replication; Humans
PubMed: 29242409
DOI: 10.18632/aging.101348 -
Nature Communications Oct 2022The pathways involved in suppressing DNA replication stress and the associated DNA damage are critical to maintaining genome integrity. The Mre11 complex is unique among...
The pathways involved in suppressing DNA replication stress and the associated DNA damage are critical to maintaining genome integrity. The Mre11 complex is unique among double strand break (DSB) repair proteins for its association with the DNA replication fork. Here we show that Mre11 complex inactivation causes DNA replication stress and changes in the abundance of proteins associated with nascent DNA. One of the most highly enriched proteins at the DNA replication fork upon Mre11 complex inactivation was the ubiquitin like protein ISG15. Mre11 complex deficiency and drug induced replication stress both led to the accumulation of cytoplasmic DNA and the subsequent activation of innate immune signaling via cGAS-STING-Tbk1. This led to ISG15 induction and protein ISGylation, including constituents of the replication fork. ISG15 plays a direct role in preventing replication stress. Deletion of ISG15 was associated with replication fork stalling, tonic ATR activation, genomic aberrations, and sensitivity to aphidicolin. These data reveal a previously unrecognized role for ISG15 in mitigating DNA replication stress and promoting genomic stability.
Topics: Aphidicolin; DNA; DNA Damage; DNA Repair; DNA Replication; Nucleotidyltransferases; Ubiquitins
PubMed: 36216822
DOI: 10.1038/s41467-022-33535-y -
Advances in Experimental Medicine and... 2017Organisms within the archaeal domain of life possess a simplified version of the eukaryotic DNA replication machinery. While some archaea possess a bacterial-like mode... (Review)
Review
Organisms within the archaeal domain of life possess a simplified version of the eukaryotic DNA replication machinery. While some archaea possess a bacterial-like mode of DNA replication with single origins of replication per chromosome, the majority of species characterized to date possess chromosomes with multiple replication origins. Genetic, structural, and biochemical studies have revealed the nature of archaeal origin specification. Recent work has begun to shed light on the mechanisms of replication initiation in these organisms.
Topics: Archaea; Archaeal Proteins; Chromosomes; DNA Replication; Replication Origin
PubMed: 29357055
DOI: 10.1007/978-981-10-6955-0_5