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DNA Damage and Repair at the Crossroad with Telomeres
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DNA Damage and Repair at the Crossroad with Telomeres

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (5 November 2023) | Viewed by 12935

Special Issue Editor

Dr. Gaëlle Pennarun

E-Mail Website
Guest Editor
1. Université Paris Cité, INSERM, CEA, Stabilité Génétique Cellules Souches et Radiations, F-92260 Fontenay-aux-Roses, France
2. Université Paris-Saclay, INSERM, CEA, Stabilité Génétique Cellules Souches et Radiations, F-92260 Fontenay-aux-Roses, France
Interests: telomere; nuclear envelope; lamins; senescence; DNA damage response; chromosome stability

Special Issue Information

Dear Colleagues,

Telomeres, which constitute the very ends of linear chromosomes, are essential for preserving genome stability in a wide range of eukaryotic organisms. Telomeres are capped by a specific telomere multiprotein complex that plays a key role in stabilizing and protecting chromosomes from degradation and recombination. In addition, over the past several years, several additional factors have been identified as being involved in telomere maintenance, including proteins from DNA damage signaling, repair and replication pathways. Some aspects of these mechanisms of telomere maintenance have been conserved throughout evolution. Telomere maintenance is crucial for cell growth and survival. Dysfunctional telomeres induce a DNA-damage-like response leading to cell-cycle arrest, genomic instability, senescence or cell death. Importantly, the deregulation of telomere maintenance has been linked to cancer genesis and premature aging. Furthermore, telomeric DNA, due to its highly G-rich content, is highly sensitive to oxidative stress and is vulnerable to different injuries, such as the unwanted formation of G-quadruplexes. Thus, a better understanding of mechanisms which could lead to DNA damage at telomeres, and in turn the identification of additional actors involved in their repair to avoid genome instability, are essential. In this view, telomere dynamics and their interplay with the nuclear envelope have brought new insight into the mechanisms of telomere maintenance.

In this Special Issue we aim to collect original research articles or reviews related to the DNA damage and repair at telomeres that contribute to bringing new highlights and novel findings. We especially welcome studies on a wide variety of eukaryotes, from yeasts to humans (including Arabidopsis and Drosophila), and those with a special focus on the dynamics of telomeres and their links with the nuclear envelope.

We look forward to receiving your contributions.

Dr. Gaëlle Pennarun
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • telomeres
  • DNA repair
  • DNA damage response
  • genome instability
  • senescence
  • nuclear envelope
  • evolution
  • cancer

Published Papers (4 papers)

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Review

15 pages, 1062 KiB  
Review
ATRX/DAXX: Guarding the Genome against the Hazards of ALT
by Sarah F. Clatterbuck Soper and Paul S. Meltzer
Genes 2023, 14(4), 790; https://doi.org/10.3390/genes14040790 - 24 Mar 2023
Cited by 2 | Viewed by 2526
Abstract
Proliferating cells must enact a telomere maintenance mechanism to ensure genomic stability. In a subset of tumors, telomeres are maintained not by telomerase, but through a homologous recombination-based mechanism termed Alternative Lengthening of Telomeres or ALT. The ALT process is linked to mutations [...] Read more.
Proliferating cells must enact a telomere maintenance mechanism to ensure genomic stability. In a subset of tumors, telomeres are maintained not by telomerase, but through a homologous recombination-based mechanism termed Alternative Lengthening of Telomeres or ALT. The ALT process is linked to mutations in the ATRX/DAXX/H3.3 histone chaperone complex. This complex is responsible for depositing non-replicative histone variant H3.3 at pericentric and telomeric heterochromatin but has also been found to have roles in ameliorating replication in repeat sequences and in promoting DNA repair. In this review, we will discuss ways in which ATRX/DAXX helps to protect the genome, and how loss of this complex allows ALT to take hold. Full article
(This article belongs to the Special Issue DNA Damage and Repair at the Crossroad with Telomeres)
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22 pages, 1526 KiB  
Review
Close Ties between the Nuclear Envelope and Mammalian Telomeres: Give Me Shelter
by Gaëlle Pennarun, Julien Picotto and Pascale Bertrand
Genes 2023, 14(4), 775; https://doi.org/10.3390/genes14040775 - 23 Mar 2023
Cited by 3 | Viewed by 2362
Abstract
The nuclear envelope (NE) in eukaryotic cells is essential to provide a protective compartment for the genome. Beside its role in connecting the nucleus with the cytoplasm, the NE has numerous important functions including chromatin organization, DNA replication and repair. NE alterations have [...] Read more.
The nuclear envelope (NE) in eukaryotic cells is essential to provide a protective compartment for the genome. Beside its role in connecting the nucleus with the cytoplasm, the NE has numerous important functions including chromatin organization, DNA replication and repair. NE alterations have been linked to different human diseases, such as laminopathies, and are a hallmark of cancer cells. Telomeres, the ends of eukaryotic chromosomes, are crucial for preserving genome stability. Their maintenance involves specific telomeric proteins, repair proteins and several additional factors, including NE proteins. Links between telomere maintenance and the NE have been well established in yeast, in which telomere tethering to the NE is critical for their preservation and beyond. For a long time, in mammalian cells, except during meiosis, telomeres were thought to be randomly localized throughout the nucleus, but recent advances have uncovered close ties between mammalian telomeres and the NE that play important roles for maintaining genome integrity. In this review, we will summarize these connections, with a special focus on telomere dynamics and the nuclear lamina, one of the main NE components, and discuss the evolutionary conservation of these mechanisms. Full article
(This article belongs to the Special Issue DNA Damage and Repair at the Crossroad with Telomeres)
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20 pages, 1252 KiB  
Review
Telomere Length Changes in Cancer: Insights on Carcinogenesis and Potential for Non-Invasive Diagnostic Strategies
by Zuzana Holesova, Lucia Krasnicanova, Rami Saade, Ondrej Pös, Jaroslav Budis, Juraj Gazdarica, Vanda Repiska and Tomas Szemes
Genes 2023, 14(3), 715; https://doi.org/10.3390/genes14030715 - 14 Mar 2023
Cited by 8 | Viewed by 3855
Abstract
Telomere dynamics play a crucial role in the maintenance of chromosome integrity; changes in telomere length may thus contribute to the development of various diseases including cancer. Understanding the role of telomeric DNA in carcinogenesis and detecting the presence of cell-free telomeric DNA [...] Read more.
Telomere dynamics play a crucial role in the maintenance of chromosome integrity; changes in telomere length may thus contribute to the development of various diseases including cancer. Understanding the role of telomeric DNA in carcinogenesis and detecting the presence of cell-free telomeric DNA (cf-telDNA) in body fluids offer a potential biomarker for novel cancer screening and diagnostic strategies. Liquid biopsy is becoming increasingly popular due to its undeniable benefits over conventional invasive methods. However, the organization and function of cf-telDNA in the extracellular milieu are understudied. This paper provides a review based on 3,398,017 cancer patients, patients with other conditions, and control individuals with the aim to shed more light on the inconsistent nature of telomere lengthening/shortening in oncological contexts. To gain a better understanding of biological factors (e.g., telomerase activation, alternative lengthening of telomeres) affecting telomere homeostasis across different types of cancer, we summarize mechanisms responsible for telomere length maintenance. In conclusion, we compare tissue- and liquid biopsy-based approaches in cancer assessment and provide a brief outlook on the methodology used for telomere length evaluation, highlighting the advances of state-of-the-art approaches in the field. Full article
(This article belongs to the Special Issue DNA Damage and Repair at the Crossroad with Telomeres)
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Graphical abstract

18 pages, 1711 KiB  
Review
TERRA and Telomere Maintenance in the Yeast Saccharomyces cerevisiae
by Bechara Zeinoun, Maria Teresa Teixeira and Aurélia Barascu
Genes 2023, 14(3), 618; https://doi.org/10.3390/genes14030618 - 28 Feb 2023
Cited by 4 | Viewed by 2872
Abstract
Telomeres are structures made of DNA, proteins and RNA found at the ends of eukaryotic linear chromosomes. These dynamic nucleoprotein structures protect chromosomal tips from end-to-end fusions, degradation, activation of damage checkpoints and erroneous DNA repair events. Telomeres were thought to be transcriptionally [...] Read more.
Telomeres are structures made of DNA, proteins and RNA found at the ends of eukaryotic linear chromosomes. These dynamic nucleoprotein structures protect chromosomal tips from end-to-end fusions, degradation, activation of damage checkpoints and erroneous DNA repair events. Telomeres were thought to be transcriptionally silent regions because of their constitutive heterochromatin signature until telomeric long non-coding RNAs (LncRNAs) were discovered. One of them, TERRA (TElomeric Repeat-containing RNA), starts in the subtelomeric regions towards the chromosome ends from different telomeres and has been extensively studied in many evolutionarily distant eukaryotes. Changes in TERRA’s expression can lead to telomeric dysfunction, interfere with the replicative machinery and impact telomere length. TERRA also co-localizes in vivo with telomerase, and can form RNA:DNA hybrid structures called R-loops, which have been implicated in the onset of senescence and the alternative lengthening of telomere (ALT) pathway. Yet, the molecular mechanisms involving TERRA, as well as its function, remain elusive. Here, we review the current knowledge of TERRA transcription, structure, expression, regulation and its multiple telomeric and extra-telomeric functions in the budding yeast Saccharomyces cerevisiae. Full article
(This article belongs to the Special Issue DNA Damage and Repair at the Crossroad with Telomeres)
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