Role of DNA damage and repair mechanisms in uterine fibroid/leiomyomas: a review

2020 ◽  
Author(s):  
Sneh M Toprani ◽  
Varsha Kelkar Mane
Keyword(s):  
Dna Damage ◽  
Molecular Mechanisms ◽  
Healthcare Sector ◽  
Clinical Aspects ◽  
Dna Damage And Repair ◽  
Myometrial Cells ◽  
Mutational Burden ◽  
The World ◽  
Repair Mechanisms

Abstract There has been a significant annual increase in the number of cases of uterine leiomyomas or fibroids (UF) among women of all races and ages across the world. A fortune is usually spent by the healthcare sector for fibroid-related treatments and management. Molecular studies have established the higher mutational heterogeneity in UF as compared to normal myometrial cells. The contribution of DNA damage and defects in repair responses further increases the mutational burden on the cells. This in turn leads to genetic instability, associated with cancer risk and other adverse reproductive health outcomes. Such and many more growing bodies of literature have highlighted the genetic/molecular, biochemical and clinical aspects of UF; none the less there appear to be a lacuna bridging the bench to bed gap in addressing and preventing this disease. Presented here is an exhaustive review of not only the molecular mechanisms underlying the predisposition to the disease but also possible strategies to effectively diagnose, prevent, manage, and treat this disease.

scholarly journals DNA Damage Response in Multiple Myeloma: The Role of the Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 504
Author(s):  
Takayuki Saitoh ◽  
Tsukasa Oda
Keyword(s):  
Multiple Myeloma ◽  
Dna Damage ◽  
Dna Repair ◽  
Tumor Microenvironment ◽  
Dna Damage Response ◽  
Genetic Instability ◽  
Dna Repair Mechanisms ◽  
Damage Response ◽  
Repair Mechanisms

Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by genomic instability. MM cells present various forms of genetic instability, including chromosomal instability, microsatellite instability, and base-pair alterations, as well as changes in chromosome number. The tumor microenvironment and an abnormal DNA repair function affect genetic instability in this disease. In addition, states of the tumor microenvironment itself, such as inflammation and hypoxia, influence the DNA damage response, which includes DNA repair mechanisms, cell cycle checkpoints, and apoptotic pathways. Unrepaired DNA damage in tumor cells has been shown to exacerbate genomic instability and aberrant features that enable MM progression and drug resistance. This review provides an overview of the DNA repair pathways, with a special focus on their function in MM, and discusses the role of the tumor microenvironment in governing DNA repair mechanisms.

scholarly journals O21 - The role of DNA damage and repair in allergic airway inflammation

2014 ◽  
Vol 4 (Suppl 1) ◽  
pp. O21
Author(s):  
Tze Khee Chan ◽  
Xin Yi Loh ◽  
Daniel WS Tan ◽  
Bevin P Engelward ◽  
Fred WS Wong
Keyword(s):  
Dna Damage ◽  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Dna Damage And Repair

scholarly journals Evolving Role of Genomics in Genitourinary Neoplasms

2019 ◽  
Vol 48 (1) ◽  
pp. 68
Author(s):  
Michael E. Devitt ◽  
Robert Dreicer
Keyword(s):  
Dna Damage ◽  
Genomic Data ◽  
Treatment Decisions ◽  
Response To Therapy ◽  
Genomic Alterations ◽  
Dna Damage And Repair ◽  
Genitourinary Cancer ◽  
Genitourinary Cancers ◽  
The Impact

<p>The aim of this article is to review the current role of genomic testing in the risk, prognosis, and treatment of genitourinary malignancies. The authors selected guidelines, publications, and abstracts relevant to the current and emerging role of genomics in genitourinary cancers. The risk of developing genitourinary cancer can be stratified based on genomic data. Prostate cancer has the strongest degree of heritability, with <em>BRCA1/2 </em>and <em>HOXB13 </em>mutations playing a role in familial disease. Genomic data is on the verge of informing treatment decisions across genitourinary cancers. mCRPC has diverse genomic alterations that represent potential therapeutic targets, including alterations in the AR pathway, DNA damage and repair pathways, cell cycle pathways, PI3K pathway, and Wnt signaling. Genomic alterations in clear cell renal cell carcinoma can inform prognosis and mutations in mTOR pathways predict response to mTOR inhibitors. Urothelial carcinoma can be classified into different subtypes based on gene expression profiling, which provides prognostic information and predicts response to chemotherapy and immunotherapy. Specific mutations have been identified that predict response to therapy including <em>ERCC2 </em>mutations and cisplatin, DNA damage and repair mutations and checkpoint inhibitors, and <em>FGFR3 </em>mutations and FGFR tyrosine kinase inhibitors such as erdafitinib.</p><p><strong>Conclusion. </strong>Genitourinary malignancies have not felt the impact of genomic data as greatly as other cancer types. The majority of benefit lies in identifying patients at high risk of genitourinary cancer. Fortunately, breakthroughs are on the horizon that will result in a greater incorporation of genomic information into treatment decisions for patients with genitourinary cancer.</p>

scholarly journals Arsenic Biotransformation as a Cancer Promoting Factor by Inducing DNA Damage and Disruption of Repair Mechanisms

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Victor D. Martinez ◽  
Emily A. Vucic ◽  
Marta Adonis ◽  
Lionel Gil ◽  
Wan L. Lam
Keyword(s):  
Dna Damage ◽  
Drinking Water ◽  
Repair Process ◽  
Dna Methyltransferases ◽  
Health Concern ◽  
Dna Damage And Repair ◽  
Repair Mechanisms ◽  
Contaminated Drinking Water ◽  
High Concentrations ◽  
Epigenetic Patterns

Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM). Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells, arsenic is also postulated to affect maintenance of normal DNA methylation patterns, chromatin structure, and genomic stability. The biological processes underlying the cancer promoting factors of arsenic metabolism, related to DNA damage and repair, will be discussed here.

Cancer epidemiology and public health

2021 ◽  
pp. 17-42
Author(s):  
Paolo Boffetta ◽  
Zuo-Feng Zhang ◽  
Carlo La Vecchia
Keyword(s):  
Public Health ◽  
Risk Factors ◽  
Molecular Mechanisms ◽  
Cancer Epidemiology ◽  
Attributable Risk ◽  
World Population ◽  
The World ◽  
Near Future ◽  
Epidemiology And Public Health

Neoplasms continue to dominate globally as one of the major sources of human disease and death. There are multiple modifiable causes of cancer and understanding their attributable risk factors for each cancer is of importance. This chapter covers the role of cellular and molecular mechanisms as well as the experimental and epidemiological approaches as determinants of the main cancers. Even if major discoveries in the clinical management of cancer patients will be accomplished in the near future, the changes will mainly affect the affluent part of the world population. Promising approaches focused on prevention of the known causes, reducing its consequences, notably in resource-constrained settings are highlighted.

Molecular Interactions of α-Synuclein, Mitochondria, and Cellular Degradation Pathways in Parkinson's Disease

2020 ◽  
pp. 212-234
Author(s):  
Mansi Verma ◽  
Sujata Basu ◽  
Manisha Singh ◽  
Rachana R. ◽  
Simrat Kaur ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Interactions ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Degradation Pathways ◽  
Functional Changes ◽  
The World ◽  
Novel Therapeutic

Parkinson's disease (PD) has been reported to be the most common neurodegenerative diseases all over the world. Several proteins are associated and responsible for causing PD. One such protein is α-synuclein. This chapter discusses the role of α-synuclein in PD. Various genetic and epigenetic factors, which cause structural and functional changes for α-synuclein, have been described. Several molecular mechanisms, which are involved in regulating mitochondrial and lysosomal related pathways and are linked to α-synuclein, have been discussed in detail. The knowledge gathered is further discussed in terms of using α-synuclein as a diagnostic marker for PD and as a novel therapeutic target for the same.

scholarly journals Mechanisms of replication and repair in mitochondrial DNA deletion formation

2020 ◽  
Vol 48 (20) ◽  
pp. 11244-11258
Author(s):  
Gabriele A Fontana ◽  
Hailey L Gahlon
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Mitochondrial Dna Deletion ◽  
Deletion Formation ◽  
Dna Deletion ◽  
Mtdna Deletions ◽  
Mtdna Deletion

Abstract Deletions in mitochondrial DNA (mtDNA) are associated with diverse human pathologies including cancer, aging and mitochondrial disorders. Large-scale deletions span kilobases in length and the loss of these associated genes contributes to crippled oxidative phosphorylation and overall decline in mitochondrial fitness. There is not a united view for how mtDNA deletions are generated and the molecular mechanisms underlying this process are poorly understood. This review discusses the role of replication and repair in mtDNA deletion formation as well as nucleic acid motifs such as repeats, secondary structures, and DNA damage associated with deletion formation in the mitochondrial genome. We propose that while erroneous replication and repair can separately contribute to deletion formation, crosstalk between these pathways is also involved in generating deletions.

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