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Life
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Telomere and Heterochromatin Biology in Ageing and Disease
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Telomere and Heterochromatin Biology in Ageing and Disease

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: closed (8 January 2021) | Viewed by 6874

Special Issue Editor

Dr. Aaron Mendez-Bermudez

E-Mail Website1 Website2
Guest Editor
1. School of Medicine, CNRS, INSERM, IRCAN, Université Côte d'Azur, 06103 Nice, France
2. International Research Laboratory for Hematology, Cancer and Aging, Shanghai Ruijin Hospital, Shanghai Jiaotong University and Côte-d'Azur University, Shanghai, China
Interests: cellular senescence; telomere biology; heterochromatin; DNA replication; recombination and repair

Special Issue Information

Ageing can be described as the accumulation of changes experimented over the life of an organism. It is thought than the accumulation of senescent cells in tissues leads to organ deterioration and ultimately to age-related pathologies such as atherosclerosis, arthritis, osteoporosis, type 2 diabetes, and cancer, amongst others. 

In recent years, the understanding of the cellular and molecular mechanisms leading to senescence has significantly progressed. Many players are interconnected in this process. Among them, telomeres, sometimes referred as the biological clock of the cells, have been paid special attention due to their role in modulating the life span of the cells. More recently, heterochromatin was found to play significant roles in the nuclear organization and gene expression changes occurring in this biological process.

This Special Issue aims to gather novel findings on telomere and heterochromatin biology, ranging from DNA replication, recombination, and repair to nuclear organization and gene expression, with a special focus on ageing and age-related pathologies.

Dr. Aaron Mendez-Bermudez
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. Life 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

  • DNA replication, repair and recombination
  • telomeres
  • heterochromatin
  • cellular senescence
  • ageing
  • age-related pathologies

Published Papers (3 papers)

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Research

16 pages, 12231 KiB  
Article
Epigenetic Characteristics of Human Subtelomeres Vary in Cells Utilizing the Alternative Lengthening of Telomeres (ALT) Pathway
by Shir Toubiana, Aya Tzur-Gilat and Sara Selig
Life 2021, 11(4), 278; https://doi.org/10.3390/life11040278 - 26 Mar 2021
Cited by 2 | Viewed by 2337
Abstract
Most human cancers circumvent senescence by activating a telomere length maintenance mechanism, most commonly involving telomerase activation. A minority of cancers utilize the recombination-based alternative lengthening of telomeres (ALT) pathway. The exact requirements for unleashing normally repressed recombination at telomeres are yet unclear. [...] Read more.
Most human cancers circumvent senescence by activating a telomere length maintenance mechanism, most commonly involving telomerase activation. A minority of cancers utilize the recombination-based alternative lengthening of telomeres (ALT) pathway. The exact requirements for unleashing normally repressed recombination at telomeres are yet unclear. Epigenetic modifications at telomeric regions were suggested to be pivotal for activating ALT; however, conflicting data exist regarding their exact nature and necessity. To uncover common ALT-positive epigenetic characteristics, we performed a comprehensive analysis of subtelomeric DNA methylation, histone modifications, and TERRA expression in several ALT-positive and ALT-negative cell lines. We found that subtelomeric DNA methylation does not differentiate between the ALT-positive and ALT-negative groups, and most of the analyzed subtelomeres within each group do not share common DNA methylation patterns. Additionally, similar TERRA levels were measured in the ALT-positive and ALT-negative groups, and TERRA levels varied significantly among the members of the ALT-positive group. Subtelomeric H3K4 and H3K9 trimethylation also differed significantly between samples in the ALT-positive group. Our findings do not support a common route by which epigenetic modifications activate telomeric recombination in ALT-positive cells, and thus, different therapeutic approaches will be necessary to overcome ALT-dependent cellular immortalization. Full article
(This article belongs to the Special Issue Telomere and Heterochromatin Biology in Ageing and Disease)
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8 pages, 1405 KiB  
Article
The Telomeric Protein TRF2 Regulates Replication Origin Activity within Pericentromeric Heterochromatin
by Serge Bauwens, Liudmyla Lototska, Stephane Koundrioukoff, Michelle Debatisse, Jing Ye, Eric Gilson and Aaron Mendez-Bermudez
Life 2021, 11(4), 267; https://doi.org/10.3390/life11040267 - 24 Mar 2021
Cited by 7 | Viewed by 2169
Abstract
Heterochromatic regions render the replication process particularly difficult due to the high level of chromatin compaction and the presence of repeated DNA sequences. In humans, replication through pericentromeric heterochromatin requires the binding of a complex formed by the telomeric factor TRF2 and the [...] Read more.
Heterochromatic regions render the replication process particularly difficult due to the high level of chromatin compaction and the presence of repeated DNA sequences. In humans, replication through pericentromeric heterochromatin requires the binding of a complex formed by the telomeric factor TRF2 and the helicase RTEL1 in order to relieve topological barriers blocking fork progression. Since TRF2 is known to bind the Origin Replication Complex (ORC), we hypothesized that this factor could also play a role at the replication origins (ORI) of these heterochromatin regions. By performing DNA combing analysis, we found that the ORI density is higher within pericentromeric satellite DNA repeats than within bulk genomic DNA and decreased upon TRF2 downregulation. Moreover, we showed that TRF2 and ORC2 interact in pericentromeric DNA, providing a mechanism by which TRF2 is involved in ORI activity. Altogether, our findings reveal an essential role for TRF2 in pericentromeric heterochromatin replication by regulating both replication initiation and elongation. Full article
(This article belongs to the Special Issue Telomere and Heterochromatin Biology in Ageing and Disease)
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10 pages, 2040 KiB  
Article
Telomere Instability in Lynch Syndrome Families Leads to Some Shorter Telomeres in MSH2+/- Carriers
by M. Carmen Garrido-Navas, Frances Tippins, Julian Barwell, Jonathan Hoffman, Veryan Codd and Nicola J. Royle
Life 2020, 10(11), 265; https://doi.org/10.3390/life10110265 - 31 Oct 2020
Cited by 2 | Viewed by 1822
Abstract
Lynch syndrome (LS) is an inherited predisposition to early onset of various cancers, caused by mutation in a DNA mismatch repair (MMR) gene. In heterozygous MMR+/− carriers, somatic mutation, loss or silencing of the wild type allele increases the mutation rate, facilitating [...] Read more.
Lynch syndrome (LS) is an inherited predisposition to early onset of various cancers, caused by mutation in a DNA mismatch repair (MMR) gene. In heterozygous MMR+/− carriers, somatic mutation, loss or silencing of the wild type allele increases the mutation rate, facilitating the initiation of MMR-defective cancers. These cancers are characterized by instability at short tandem repeats (STRs) and in telomeric DNA. We have investigated telomere length in saliva DNA from LS and control families, using single telomere analysis at XpYp and 12q and by qPCR to measure total telomeric DNA. Single telomere analysis showed a trend for shorter XpYp telomeres in MSH2+/− carriers compared to MLH1+/− carriers or controls, but this was masked in the comparative analysis of total telomeric DNA. Comparison of age-adjusted telomere length within families showed that neither MSH2+/− or MLH1+/− children had consistently shorter or longer telomeres than their MMR+/− parent, indicating the absence of an inter-generational effect on telomere length. Unexpectedly however, wildtype children in families with MSH2 mutations, had significantly longer XpYp telomeres than their MMR+/− parent. Altogether our data suggest that MMR insufficiency, particularly in MSH2+/− carriers, increases telomere instability and somatic cell turnover during the lifetime of LS mutation carriers but has minimal consequences for telomere length in the germline. Full article
(This article belongs to the Special Issue Telomere and Heterochromatin Biology in Ageing and Disease)
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