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Biomolecules
Special Issues
Role of Telomere Dynamics in Chromosome Stability and Transcriptional Regulation
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Role of Telomere Dynamics in Chromosome Stability and Transcriptional Regulation

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biomacromolecules: Nucleic Acids".

Deadline for manuscript submissions: closed (20 November 2023) | Viewed by 5947

Special Issue Editor

Prof. Dr. Arthur J. Lustig

E-Mail Website
Guest Editor
School of Medicine, Tulane University, New Orleans, LA, USA
Interests: telomeres; chromatin; recombination
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Telomeres are specialized structures located at the ends of chromosomes that solve the end-replication problem and protect termini from degradation and fusion. Telomere length is maintained by the enzyme telomerase, and the shortening of telomeres has been associated with aging and disease states. Telomere integrity is central to the maintenance of genetic stability. Telomeres and subtelomeric regions have been implicated in processes ranging from homologous recombination to chromosome fragmentation. In addition to their role in chromosome stability, telomeres also play crucial roles in the regulation of transcriptional regulation of both coding and non-coding TERRA RNAs through processes such as telomere position effects and higher-order chromosome structure.  We invite papers and reviews in areas related to the role of telomeres in chromosome stability and transcriptional regulation.

Prof. Dr. Arthur J. Lustig
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. Biomolecules 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 2700 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.

Published Papers (3 papers)

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Review

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22 pages, 4831 KiB  
Review
Guardians of the Genome: How the Single-Stranded DNA-Binding Proteins RPA and CST Facilitate Telomere Replication
by Conner L. Olson and Deborah S. Wuttke
Biomolecules 2024, 14(3), 263; https://doi.org/10.3390/biom14030263 - 22 Feb 2024
Viewed by 1644
Abstract
Telomeres act as the protective caps of eukaryotic linear chromosomes; thus, proper telomere maintenance is crucial for genome stability. Successful telomere replication is a cornerstone of telomere length regulation, but this process can be fraught due to the many intrinsic challenges telomeres pose [...] Read more.
Telomeres act as the protective caps of eukaryotic linear chromosomes; thus, proper telomere maintenance is crucial for genome stability. Successful telomere replication is a cornerstone of telomere length regulation, but this process can be fraught due to the many intrinsic challenges telomeres pose to the replication machinery. In addition to the famous “end replication” problem due to the discontinuous nature of lagging strand synthesis, telomeres require various telomere-specific steps for maintaining the proper 3′ overhang length. Bulk telomere replication also encounters its own difficulties as telomeres are prone to various forms of replication roadblocks. These roadblocks can result in an increase in replication stress that can cause replication forks to slow, stall, or become reversed. Ultimately, this leads to excess single-stranded DNA (ssDNA) that needs to be managed and protected for replication to continue and to prevent DNA damage and genome instability. RPA and CST are single-stranded DNA-binding protein complexes that play key roles in performing this task and help stabilize stalled forks for continued replication. The interplay between RPA and CST, their functions at telomeres during replication, and their specialized features for helping overcome replication stress at telomeres are the focus of this review. Full article
(This article belongs to the Special Issue Role of Telomere Dynamics in Chromosome Stability and Transcriptional Regulation)
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25 pages, 1923 KiB  
Review
Unwrap RAP1’s Mystery at Kinetoplastid Telomeres
by Bibo Li
Biomolecules 2024, 14(1), 67; https://doi.org/10.3390/biom14010067 - 4 Jan 2024
Viewed by 2338
Abstract
Although located at the chromosome end, telomeres are an essential chromosome component that helps maintain genome integrity and chromosome stability from protozoa to mammals. The role of telomere proteins in chromosome end protection is conserved, where they suppress various DNA damage response machineries [...] Read more.
Although located at the chromosome end, telomeres are an essential chromosome component that helps maintain genome integrity and chromosome stability from protozoa to mammals. The role of telomere proteins in chromosome end protection is conserved, where they suppress various DNA damage response machineries and block nucleolytic degradation of the natural chromosome ends, although the detailed underlying mechanisms are not identical. In addition, the specialized telomere structure exerts a repressive epigenetic effect on expression of genes located at subtelomeres in a number of eukaryotic organisms. This so-called telomeric silencing also affects virulence of a number of microbial pathogens that undergo antigenic variation/phenotypic switching. Telomere proteins, particularly the RAP1 homologs, have been shown to be a key player for telomeric silencing. RAP1 homologs also suppress the expression of Telomere Repeat-containing RNA (TERRA), which is linked to their roles in telomere stability maintenance. The functions of RAP1s in suppressing telomere recombination are largely conserved from kinetoplastids to mammals. However, the underlying mechanisms of RAP1-mediated telomeric silencing have many species-specific features. In this review, I will focus on Trypanosoma brucei RAP1’s functions in suppressing telomeric/subtelomeric DNA recombination and in the regulation of monoallelic expression of subtelomere-located major surface antigen genes. Common and unique mechanisms will be compared among RAP1 homologs, and their implications will be discussed. Full article
(This article belongs to the Special Issue Role of Telomere Dynamics in Chromosome Stability and Transcriptional Regulation)
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Other

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14 pages, 1753 KiB  
Perspective
Alternative Lengthening of Telomeres in Yeast: Old Questions and New Approaches
by Kendra Musmaker, Jacob Wells, Meng-Chia Tsai, Josep M. Comeron and Anna Malkova
Biomolecules 2024, 14(1), 113; https://doi.org/10.3390/biom14010113 - 16 Jan 2024
Viewed by 1648
Abstract
Alternative lengthening of telomeres (ALT) is a homologous recombination-based pathway utilized by 10–15% of cancer cells that allows cells to maintain their telomeres in the absence of telomerase. This pathway was originally discovered in the yeast Saccharomyces cerevisiae and, for decades, yeast has [...] Read more.
Alternative lengthening of telomeres (ALT) is a homologous recombination-based pathway utilized by 10–15% of cancer cells that allows cells to maintain their telomeres in the absence of telomerase. This pathway was originally discovered in the yeast Saccharomyces cerevisiae and, for decades, yeast has served as a robust model to study ALT. Using yeast as a model, two types of ALT (RAD51-dependent and RAD51-independent) have been described. Studies in yeast have provided the phenotypic characterization of ALT survivors, descriptions of the proteins involved, and implicated break-induced replication (BIR) as the mechanism responsible for ALT. Nevertheless, many questions have remained, and answering them has required the development of new quantitative methods. In this review we discuss the historic aspects of the ALT investigation in yeast as well as new approaches to investigating ALT, including ultra-long sequencing, computational modeling, and the use of population genetics. We discuss how employing new methods contributes to our current understanding of the ALT mechanism and how they may expand our understanding of ALT in the future. Full article
(This article belongs to the Special Issue Role of Telomere Dynamics in Chromosome Stability and Transcriptional Regulation)
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