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Biomolecules
Special Issues
Genome Maintenance Systems: Small Molecule Modulators, Mechanisms, Regulation and Clinical...
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Genome Maintenance Systems: Small Molecule Modulators, Mechanisms, Regulation and Clinical Implications

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

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 24888

Special Issue Editor

Prof. Dr. Tae-Hong Kang

E-Mail Website
Guest Editor
Department of Biomedical Sciences, College of Natural Science, Dong-A University, Busan 49315, Republic of Korea
Interests: DNA damage; DNA repair; DNA replication; cell cycle checkpoint; circadian clock; nucleotide excision repair; ATR pathway
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Genomic instability is a crucial driving force of the onset and progression of two major human disorders, cancer and aging, which can arise owing to defects in the DNA damage response and/or increased replication stress. In order to maintain genomic stability and proper cell function, timely relief of the stresses on the DNA double helix by the DNA caretaking systems is essential. It is evident that the better our understating into the genome maintenance systems is, the more it will pave the way for us to prevent and treat the aforementioned diseases. Indeed, a promising concept of precision medicine for cancer treatment, synthetic lethality, has been turned out to be very useful for certain types of cancer patients in clinics. Our ongoing endeavors toward uncovering the precise molecular mechanism underlying genome maintenance should also uncover new paradigms for prevention, diagnosis, and rational therapy.

This Special Issue aims to highlight the recent progress of the development of small molecule modulators, the discovery of novel factors and regulatory mechanisms of the genome maintenance systems encompassing DNA repair, checkpoint, cell death, as well as crosstalk between the systems. Reviews or articles on the molecular targets for synthetic lethality and strategies for personalized precision cancer therapy based on the genome stability control are also welcome to consider for publication.

Dr. Tae-Hong Kang
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.

Keywords

  • Genomic stability
  • DNA repair system
  • DNA damage response
  • Synthetic lethality
  • Replication stress
  • Checkpoint
  • Aging
  • Cell death
  • Cancer therapy
  • Human disorders

Published Papers (5 papers)

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Review

11 pages, 953 KiB  
Review
Circadian Rhythm of NER and ATR Pathways
by Tae-Hong Kang
Biomolecules 2021, 11(5), 715; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11050715 - 11 May 2021
Cited by 12 | Viewed by 3354
Abstract
Genomic integrity is constantly insulted by solar ultraviolet (UV) radiation. Adaptative cellular mechanisms called DNA damage responses comprising DNA repair, cell cycle checkpoint, and apoptosis, are believed to be evolved to limit genomic instability according to the photoperiod during a day. As seen [...] Read more.
Genomic integrity is constantly insulted by solar ultraviolet (UV) radiation. Adaptative cellular mechanisms called DNA damage responses comprising DNA repair, cell cycle checkpoint, and apoptosis, are believed to be evolved to limit genomic instability according to the photoperiod during a day. As seen in many other key cellular metabolisms, genome surveillance mechanisms against genotoxic UV radiation are under the control of circadian clock systems, thereby exhibiting daily oscillations in their catalytic activities. Indeed, it has been demonstrated that nucleotide excision repair (NER), the sole DNA repair mechanism correcting UV-induced DNA photolesions, and ataxia–telangiectasia-mutated and Rad3-related (ATR)-mediated cell cycle checkpoint kinase are subjected to the robust control of the circadian clock. The molecular foundation for the circadian rhythm of UV-induced DNA damage responses in mammalian cells will be discussed. Full article
(This article belongs to the Special Issue Genome Maintenance Systems: Small Molecule Modulators, Mechanisms, Regulation and Clinical Implications)
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18 pages, 2176 KiB  
Review
A Newly Assigned Role of CTCF in Cellular Response to Broken DNAs
by Mi Ae Kang and Jong-Soo Lee
Biomolecules 2021, 11(3), 363; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11030363 - 27 Feb 2021
Cited by 9 | Viewed by 3634
Abstract
Best known as a transcriptional factor, CCCTC-binding factor (CTCF) is a highly conserved multifunctional DNA-binding protein with 11 zinc fingers. It functions in diverse genomic processes, including transcriptional activation/repression, insulation, genome imprinting and three-dimensional genome organization. A big surprise has recently emerged with [...] Read more.
Best known as a transcriptional factor, CCCTC-binding factor (CTCF) is a highly conserved multifunctional DNA-binding protein with 11 zinc fingers. It functions in diverse genomic processes, including transcriptional activation/repression, insulation, genome imprinting and three-dimensional genome organization. A big surprise has recently emerged with the identification of CTCF engaging in the repair of DNA double-strand breaks (DSBs) and in the maintenance of genome fidelity. This discovery now adds a new dimension to the multifaceted attributes of this protein. CTCF facilitates the most accurate DSB repair via homologous recombination (HR) that occurs through an elaborate pathway, which entails a chain of timely assembly/disassembly of various HR-repair complexes and chromatin modifications and coordinates multistep HR processes to faithfully restore the original DNA sequences of broken DNA sites. Understanding the functional crosstalks between CTCF and other HR factors will illuminate the molecular basis of various human diseases that range from developmental disorders to cancer and arise from impaired repair. Such knowledge will also help understand the molecular mechanisms underlying the diverse functions of CTCF in genome biology. In this review, we discuss the recent advances regarding this newly assigned versatile role of CTCF and the mechanism whereby CTCF functions in DSB repair. Full article
(This article belongs to the Special Issue Genome Maintenance Systems: Small Molecule Modulators, Mechanisms, Regulation and Clinical Implications)
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17 pages, 1320 KiB  
Review
Role of Small GTPase RhoA in DNA Damage Response
by Chibin Cheng, Daniel Seen, Chunwen Zheng, Ruijie Zeng and Enmin Li
Biomolecules 2021, 11(2), 212; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11020212 - 3 Feb 2021
Cited by 18 | Viewed by 4036
Abstract
Accumulating evidence has suggested a role of the small GTPase Ras homolog gene family member A (RhoA) in DNA damage response (DDR) in addition to its traditional function of regulating cell morphology. In DDR, 2 key components of DNA repair, ataxia telangiectasia-mutated (ATM) [...] Read more.
Accumulating evidence has suggested a role of the small GTPase Ras homolog gene family member A (RhoA) in DNA damage response (DDR) in addition to its traditional function of regulating cell morphology. In DDR, 2 key components of DNA repair, ataxia telangiectasia-mutated (ATM) and flap structure-specific endonuclease 1 (FEN1), along with intracellular reactive oxygen species (ROS) have been shown to regulate RhoA activation. In addition, Rho-specific guanine exchange factors (GEFs), neuroepithelial transforming gene 1 (Net1) and epithelial cell transforming sequence 2 (Ect2), have specific functions in DDR, and they also participate in Ras-related C3 botulinum toxin substrate 1 (Rac1)/RhoA interaction, a process which is largely unappreciated yet possibly of significance in DDR. Downstream of RhoA, current evidence has highlighted its role in mediating cell cycle arrest, which is an important step in DNA repair. Unraveling the mechanism by which RhoA modulates DDR may provide more insight into DDR itself and may aid in the future development of cancer therapies. Full article
(This article belongs to the Special Issue Genome Maintenance Systems: Small Molecule Modulators, Mechanisms, Regulation and Clinical Implications)
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22 pages, 1291 KiB  
Review
Targeting Non-Oncogene Addiction for Cancer Therapy
by Hae Ryung Chang, Eunyoung Jung, Soobin Cho, Young-Jun Jeon and Yonghwan Kim
Biomolecules 2021, 11(2), 129; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11020129 - 20 Jan 2021
Cited by 10 | Viewed by 4690
Abstract
While Next-Generation Sequencing (NGS) and technological advances have been useful in identifying genetic profiles of tumorigenesis, novel target proteins and various clinical biomarkers, cancer continues to be a major global health threat. DNA replication, DNA damage response (DDR) and repair, and cell cycle [...] Read more.
While Next-Generation Sequencing (NGS) and technological advances have been useful in identifying genetic profiles of tumorigenesis, novel target proteins and various clinical biomarkers, cancer continues to be a major global health threat. DNA replication, DNA damage response (DDR) and repair, and cell cycle regulation continue to be essential systems in targeted cancer therapies. Although many genes involved in DDR are known to be tumor suppressor genes, cancer cells are often dependent and addicted to these genes, making them excellent therapeutic targets. In this review, genes implicated in DNA replication, DDR, DNA repair, cell cycle regulation are discussed with reference to peptide or small molecule inhibitors which may prove therapeutic in cancer patients. Additionally, the potential of utilizing novel synthetic lethal genes in these pathways is examined, providing possible new targets for future therapeutics. Specifically, we evaluate the potential of TONSL as a novel gene for targeted therapy. Although it is a scaffold protein with no known enzymatic activity, the strategy used for developing PCNA inhibitors can also be utilized to target TONSL. This review summarizes current knowledge on non-oncogene addiction, and the utilization of synthetic lethality for developing novel inhibitors targeting non-oncogenic addiction for cancer therapy. Full article
(This article belongs to the Special Issue Genome Maintenance Systems: Small Molecule Modulators, Mechanisms, Regulation and Clinical Implications)
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14 pages, 2461 KiB  
Review
Spironolactone and XPB: An Old Drug with a New Molecular Target
by Ryan D. Gabbard, Robert R. Hoopes and Michael G. Kemp
Biomolecules 2020, 10(5), 756; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10050756 - 13 May 2020
Cited by 19 | Viewed by 8710
Abstract
Spironolactone (SP) is commonly used for the treatment of heart failure, hypertension, and complications of cirrhosis by antagonizing the mineralocorticoid receptor. However, SP also antagonizes the androgen receptor, and thus SP has also been shown to be effective in the treatment of acne, [...] Read more.
Spironolactone (SP) is commonly used for the treatment of heart failure, hypertension, and complications of cirrhosis by antagonizing the mineralocorticoid receptor. However, SP also antagonizes the androgen receptor, and thus SP has also been shown to be effective in the treatment of acne, hair loss, and hirsutism in women. Interestingly, recent drug repurposing screens have identified new and diverse functions for SP as a simulator of tumor immunosurveillance and as an inhibitor of DNA repair and viral infection. These novel pharmacological effects of SP have all been linked to the ability of SP to induce the rapid proteolytic degradation of the xeroderma pigmentosum group B (XPB) protein. XPB is a critical enzymatic component of the multi-subunit complex known as transcription factor II-H (TFIIH), which plays essential roles in both DNA repair and the initiation of transcription. Given the critical functions for XPB and TFIIH in these processes, the loss of XPB by SP could lead to mutagenesis. However, the ability of SP to promote cancer stem cell death and facilitate immune recognition may counteract the negative consequences of SP to mitigate carcinogenic risk. Thus, SP appears to have new and interesting pharmacological effects that may extend its potential uses. Full article
(This article belongs to the Special Issue Genome Maintenance Systems: Small Molecule Modulators, Mechanisms, Regulation and Clinical Implications)
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