DNA Repair Defects and Telomere Dysfunction in Diseases

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell and Gene Therapy".

Deadline for manuscript submissions: closed (28 February 2017) | Viewed by 13497

Special Issue Editor

Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Interests: telomeres and telomerase; DNA damage and repair; toxicogenomics and environmental toxicology; radiation biology; experimental therapeutics; occupational and environmental health

Special Issue Information

Dear Colleagues,

Faithful transmission of genetic material to the next generation is one of the primary objectives of an organism. This should be attained despite the constant damage induced by endogenous and environmental agents on DNA. Evolution has invested in DNA repair mechanisms to combat the incurred DNA damage. These repair mechanisms are biologically significant in maintaining genome integrity and in turn to prevent diverse human diseases. In effective protection from DNA damage may lead to genetic instability as well. Genome instability is a hallmark of cancer cells, but are also a cause of genetic diseases in humans. Patients with genome instability/chromosome breakage syndromes show reduced DNA repair and higher disease prevalence. Telomeres have special roles in protecting the chromosomes as well as genome integrity. Telomere function may have contrasting consequences—inducing replicative senescence or promoting tumorigenesis. The roles may vary between cell types, depending on the expression of telomerase enzyme, the level of mutations present, the efficiency or deficiency of related DNA repair pathways and oxidative stress levels in the cell milieu. Telomeropathies are an emerging spectrum of human disorders, which exhibit telomere related defects. Improving our understanding of these mechanisms may provide new avenues for disease management.

This Special Issue provides the platform to publish original research as well as review articles in an Open Access format in the exciting crossroad between DNA repair and telomere dynamics. We aim for a comprehensive collection of articles, which cover either of the topics, DNA damage response/repair and/or telomere function, with special reference to human health and diseases. Studies on other models are also welcome. Articles on molecular mechanisms and the targeting of either of these pathways in theranostics would also be of major interest.

Dr. Prakash Hande
Guest Editor

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Keywords

  • genome stability
  • DNA damage
  • DNA repair
  • DNA repair defect and human diseases
  • premature ageing
  • DNA repair inhibition
  • telomeres and telomerase
  • telomere dysfunction and human diseases
  • telomeropathies
  • chromosome instability syndromes

Published Papers (2 papers)

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Review

937 KiB  
Review
Telomere Biology—Insights into an Intriguing Phenomenon
by Shriram Venkatesan, Aik Kia Khaw and Manoor Prakash Hande
Cells 2017, 6(2), 15; https://doi.org/10.3390/cells6020015 - 19 Jun 2017
Cited by 19 | Viewed by 6595
Abstract
Bacteria and viruses possess circular DNA, whereas eukaryotes with typically very large DNA molecules have had to evolve into linear chromosomes to circumvent the problem of supercoiling circular DNA of that size. Consequently, such organisms possess telomeres to cap chromosome ends. Telomeres are [...] Read more.
Bacteria and viruses possess circular DNA, whereas eukaryotes with typically very large DNA molecules have had to evolve into linear chromosomes to circumvent the problem of supercoiling circular DNA of that size. Consequently, such organisms possess telomeres to cap chromosome ends. Telomeres are essentially tandem repeats of any DNA sequence that are present at the ends of chromosomes. Their biology has been an enigmatic one, involving various molecules interacting dynamically in an evolutionarily well-trimmed fashion. Telomeres range from canonical hexameric repeats in most eukaryotes to unimaginably random retrotransposons, which attach to chromosome ends and reverse-transcribe to DNA in some plants and insects. Telomeres invariably associate with specialised protein complexes that envelop it, also regulating access of the ends to legitimate enzymes involved in telomere metabolism. They also transcribe into repetitive RNA which also seems to be playing significant roles in telomere maintenance. Telomeres thus form the intersection of DNA, protein, and RNA molecules acting in concert to maintain chromosome integrity. Telomere biology is emerging to appear ever more complex than previously envisaged, with the continual discovery of more molecules and interplays at the telomeres. This review also includes a section dedicated to the history of telomere biology, and intends to target the scientific audience new to the field by rendering an understanding of the phenomenon of chromosome end protection at large, with more emphasis on the biology of human telomeres. The review provides an update on the field and mentions the questions that need to be addressed. Full article
(This article belongs to the Special Issue DNA Repair Defects and Telomere Dysfunction in Diseases)
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2238 KiB  
Review
Taking a Bad Turn: Compromised DNA Damage Response in Leukemia
by Nadine Nilles and Birthe Fahrenkrog
Cells 2017, 6(2), 11; https://doi.org/10.3390/cells6020011 - 04 May 2017
Cited by 15 | Viewed by 6577
Abstract
Genomic integrity is of outmost importance for the survival at the cellular and the organismal level and key to human health. To ensure the integrity of their DNA, cells have evolved maintenance programs collectively known as the DNA damage response. Particularly challenging for [...] Read more.
Genomic integrity is of outmost importance for the survival at the cellular and the organismal level and key to human health. To ensure the integrity of their DNA, cells have evolved maintenance programs collectively known as the DNA damage response. Particularly challenging for genome integrity are DNA double-strand breaks (DSB) and defects in their repair are often associated with human disease, including leukemia. Defective DSB repair may not only be disease-causing, but further contribute to poor treatment outcome and poor prognosis in leukemia. Here, we review current insight into altered DSB repair mechanisms identified in leukemia. While DSB repair is somewhat compromised in all leukemic subtypes, certain key players of DSB repair are particularly targeted: DNA-dependent protein kinase (DNA-PK) and Ku70/80 in the non-homologous end-joining pathway, as well as Rad51 and breast cancer 1/2 (BRCA1/2), key players in homologous recombination. Defects in leukemia-related DSB repair may not only arise from dysfunctional repair components, but also indirectly from mutations in key regulators of gene expression and/or chromatin structure, such as p53, the Kirsten ras oncogene (K-RAS), and isocitrate dehydrogenase 1 and 2 (IDH1/2). A detailed understanding of the basis for defective DNA damage response (DDR) mechanisms for each leukemia subtype may allow to further develop new treatment methods to improve treatment outcome and prognosis for patients. Full article
(This article belongs to the Special Issue DNA Repair Defects and Telomere Dysfunction in Diseases)
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