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DNA Dynamics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Informatics".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 12502

Special Issue Editor


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Guest Editor
Dipartimento di Bioscienze, Università degli Studi di Milano, via Celoria 26, 20133 Milano, Italy
Interests: DNA repair; DNA replication; genome stability

Special Issue Information

Dear Colleagues,

Since the identification of the double helix structure of DNA in 1953, significant progress has been made in understanding how this fascinating molecule is able to both preserve and transmit genetic information. Sophisticated DNA replication mechanisms ensure the correct duplication of genetic information and equally specialized repair mechanisms help to address and resolve the insults suffered during normal cellular metabolism.

Beyond this remarkable stability, the double helix of DNA is an extremely dynamic molecule and it actively contributes to its multiple functions. Dynamic interaction between proteins and DNA regulate important processes such as DNA transcription and repair. Alternative DNA structures, such as the right-handed double helix proposed by Watson and Crick, can actively participate to different cellular processes. It is, for example, known that G-quadruplex DNA can regulate transcription and affects DNA replication. In addition, any process that involves opening the double helix meets the fascinating world of DNA topology.

The complex structure of chromatin in eukaryotic organisms is also a further contribution to the dynamism of DNA and actively collaborates with its primary functions. At the chromosomal level it is now evident how the spatial and temporal arrangement within the nucleus is extremely coordinated and allows a further level of regulation.

The intent of this special issue of International Journal of Molecular Sciences is to welcome papers and reviews that analyze these aspects of DNA dynamics also taking advantage of recent technologies that allow single cell analysis.

Prof. Dr. Federico Lazzaro
Guest Editor

Manuscript Submission Information

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Published Papers (4 papers)

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Research

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27 pages, 3470 KiB  
Article
Disruption of Chromatin Dynamics by Hypotonic Stress Suppresses HR and Shifts DSB Processing to Error-Prone SSA
by Lisa Marie Krieger, Emil Mladenov, Aashish Soni, Marilen Demond, Martin Stuschke and George Iliakis
Int. J. Mol. Sci. 2021, 22(20), 10957; https://doi.org/10.3390/ijms222010957 - 11 Oct 2021
Cited by 1 | Viewed by 2538
Abstract
The processing of DNA double-strand breaks (DSBs) depends on the dynamic characteristics of chromatin. To investigate how abrupt changes in chromatin compaction alter these dynamics and affect DSB processing and repair, we exposed irradiated cells to hypotonic stress (HypoS). Densitometric and chromosome-length analyses [...] Read more.
The processing of DNA double-strand breaks (DSBs) depends on the dynamic characteristics of chromatin. To investigate how abrupt changes in chromatin compaction alter these dynamics and affect DSB processing and repair, we exposed irradiated cells to hypotonic stress (HypoS). Densitometric and chromosome-length analyses show that HypoS transiently decompacts chromatin without inducing histone modifications known from regulated local chromatin decondensation, or changes in Micrococcal Nuclease (MNase) sensitivity. HypoS leaves undisturbed initial stages of DNA-damage-response (DDR), such as radiation-induced ATM activation and H2AX-phosphorylation. However, detection of ATM-pS1981, γ-H2AX and 53BP1 foci is reduced in a protein, cell cycle phase and cell line dependent manner; likely secondary to chromatin decompaction that disrupts the focal organization of DDR proteins. While HypoS only exerts small effects on classical nonhomologous end-joining (c-NHEJ) and alternative end-joining (alt-EJ), it markedly suppresses homologous recombination (HR) without affecting DNA end-resection at DSBs, and clearly enhances single-strand annealing (SSA). These shifts in pathway engagement are accompanied by decreases in HR-dependent chromatid-break repair in the G2-phase, and by increases in alt-EJ and SSA-dependent chromosomal translocations. Consequently, HypoS sensitizes cells to ionizing radiation (IR)-induced killing. We conclude that HypoS-induced global chromatin decompaction compromises regulated chromatin dynamics and genomic stability by suppressing DSB-processing by HR, and allowing error-prone processing by alt-EJ and SSA. Full article
(This article belongs to the Special Issue DNA Dynamics)
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24 pages, 4795 KiB  
Article
A Fork Trap in the Chromosomal Termination Area Is Highly Conserved across All Escherichia coli Phylogenetic Groups
by Daniel J. Goodall, Katie H. Jameson, Michelle Hawkins and Christian J. Rudolph
Int. J. Mol. Sci. 2021, 22(15), 7928; https://doi.org/10.3390/ijms22157928 - 25 Jul 2021
Cited by 3 | Viewed by 3232
Abstract
Termination of DNA replication, the final stage of genome duplication, is surprisingly complex, and failures to bring DNA synthesis to an accurate conclusion can impact genome stability and cell viability. In Escherichia coli, termination takes place in a specialised termination area opposite [...] Read more.
Termination of DNA replication, the final stage of genome duplication, is surprisingly complex, and failures to bring DNA synthesis to an accurate conclusion can impact genome stability and cell viability. In Escherichia coli, termination takes place in a specialised termination area opposite the origin. A ‘replication fork trap’ is formed by unidirectional fork barriers via the binding of Tus protein to genomic ter sites. Such a fork trap system is found in some bacterial species, but it appears not to be a general feature of bacterial chromosomes. The biochemical properties of fork trap systems have been extensively characterised, but little is known about their precise physiological roles. In this study, we compare locations and distributions of ter terminator sites in E. coli genomes across all phylogenetic groups, including Shigella. Our analysis shows that all ter sites are highly conserved in E. coli, with slightly more variability in the Shigella genomes. Our sequence analysis of ter sites and Tus proteins shows that the fork trap is likely to be active in all strains investigated. In addition, our analysis shows that the dif chromosome dimer resolution site is consistently located between the innermost ter sites, even if rearrangements have changed the location of the innermost termination area. Our data further support the idea that the replication fork trap has an important physiological role that provides an evolutionary advantage. Full article
(This article belongs to the Special Issue DNA Dynamics)
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Review

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41 pages, 2291 KiB  
Review
Spotlight on G-Quadruplexes: From Structure and Modulation to Physiological and Pathological Roles
by Maria Chiara Dell’Oca, Roberto Quadri, Giulia Maria Bernini, Luca Menin, Lavinia Grasso, Diego Rondelli, Ozge Yazici, Sarah Sertic, Federica Marini, Achille Pellicioli, Marco Muzi-Falconi and Federico Lazzaro
Int. J. Mol. Sci. 2024, 25(6), 3162; https://doi.org/10.3390/ijms25063162 - 9 Mar 2024
Viewed by 2171
Abstract
G-quadruplexes or G4s are non-canonical secondary structures of nucleic acids characterized by guanines arranged in stacked tetraplex arrays. Decades of research into these peculiar assemblies of DNA and RNA, fueled by the development and optimization of a vast array of techniques and assays, [...] Read more.
G-quadruplexes or G4s are non-canonical secondary structures of nucleic acids characterized by guanines arranged in stacked tetraplex arrays. Decades of research into these peculiar assemblies of DNA and RNA, fueled by the development and optimization of a vast array of techniques and assays, has resulted in a large amount of information regarding their structure, stability, localization, and biological significance in native systems. A plethora of articles have reported the roles of G-quadruplexes in multiple pathways across several species, ranging from gene expression regulation to RNA biogenesis and trafficking, DNA replication, and genome maintenance. Crucially, a large amount of experimental evidence has highlighted the roles of G-quadruplexes in cancer biology and other pathologies, pointing at these structurally unique guanine assemblies as amenable drug targets. Given the rapid expansion of this field of research, this review aims at summarizing all the relevant aspects of G-quadruplex biology by combining and discussing results from seminal works as well as more recent and cutting-edge experimental evidence. Additionally, the most common methodologies used to study G4s are presented to aid the reader in critically interpreting and integrating experimental data. Full article
(This article belongs to the Special Issue DNA Dynamics)
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18 pages, 7879 KiB  
Review
Transposable Elements Co-Option in Genome Evolution and Gene Regulation
by Erica Gasparotto, Filippo Vittorio Burattin, Valeria Di Gioia, Michele Panepuccia, Valeria Ranzani, Federica Marasca and Beatrice Bodega
Int. J. Mol. Sci. 2023, 24(3), 2610; https://doi.org/10.3390/ijms24032610 - 30 Jan 2023
Cited by 5 | Viewed by 3664
Abstract
The genome is no longer deemed as a fixed and inert item but rather as a moldable matter that is continuously evolving and adapting. Within this frame, Transposable Elements (TEs), ubiquitous, mobile, repetitive elements, are considered an alive portion of the genomes to [...] Read more.
The genome is no longer deemed as a fixed and inert item but rather as a moldable matter that is continuously evolving and adapting. Within this frame, Transposable Elements (TEs), ubiquitous, mobile, repetitive elements, are considered an alive portion of the genomes to date, whose functions, although long considered “dark”, are now coming to light. Here we will review that, besides the detrimental effects that TE mobilization can induce, TEs have shaped genomes in their current form, promoting genome sizing, genomic rearrangements and shuffling of DNA sequences. Although TEs are mostly represented in the genomes by evolutionarily old, short, degenerated, and sedentary fossils, they have been thoroughly co-opted by the hosts as a prolific and original source of regulatory instruments for the control of gene transcription and genome organization in the nuclear space. For these reasons, the deregulation of TE expression and/or activity is implicated in the onset and progression of several diseases. It is likely that we have just revealed the outermost layers of TE functions. Further studies on this portion of the genome are required to unlock novel regulatory functions that could also be exploited for diagnostic and therapeutic approaches. Full article
(This article belongs to the Special Issue DNA Dynamics)
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