scholarly journals The emerging role of RNAs in DNA damage repair

2017 ◽  
Vol 24 (4) ◽  
pp. 580-587 ◽  
Author(s):  
Ben R Hawley ◽  
Wei-Ting Lu ◽  
Ania Wilczynska ◽  
Martin Bushell
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Critical Role ◽  
Repair Process ◽  
Rna Molecules ◽  
Processing Enzymes ◽  
Damage Repair ◽  
New Findings ◽  
Integral Role ◽  
Repair Mechanisms

Abstract Many surveillance and repair mechanisms exist to maintain the integrity of our genome. All of the pathways described to date are controlled exclusively by proteins, which through their enzymatic activities identify breaks, propagate the damage signal, recruit further protein factors and ultimately resolve the break with little to no loss of genetic information. RNA is known to have an integral role in many cellular pathways, but, until very recently, was not considered to take part in the DNA repair process. Several reports demonstrated a conserved critical role for RNA-processing enzymes and RNA molecules in DNA repair, but the biogenesis of these damage-related RNAs and their mechanisms of action remain unknown. We will explore how these new findings challenge the idea of proteins being the sole participants in the response to DNA damage and reveal a new and exciting aspect of both DNA repair and RNA biology.

scholarly journals A Review on DNA Repair Inhibition by PARP Inhibitors in Cancer Therapy

Folia Medica ◽  
2018 ◽  
Vol 60 (1) ◽  
pp. 39-47 ◽  
Author(s):  
Ashish P. Shah ◽  
Chhagan N. Patel ◽  
Dipen K. Sureja ◽  
Kirtan P. Sanghavi
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Cancer Therapy ◽  
Repair Process ◽  
Parp Inhibitors ◽  
Brca Mutations ◽  
Development Of Resistance ◽  
Damage Repair ◽  
Future Therapy

AbstractThe DNA repair process protects the cells from DNA damaging agent by multiple pathways. Majority of the cancer therapy cause DNA damage which leads to apoptosis. The cell has natural ability to repair this damage which ultimately leads to development of resistance of drugs. The key enzymes involved in DNA repair process are poly(ADP-ribose) (PAR) and poly(ADP-ribose) polymerases (PARP). Tumor cells repair their defective gene via defective homologues recombination (HR) in the presence of enzyme PARP. PARP inhibitors inhibit the enzyme poly(ADP-ribose) polymerases (PARPs) which lead to apoptosis of cancer cells. Current clinical data shows the role of PARP inhibitors is not restricted to BRCA mutations but also effective in HR dysfunctions related tumors. Therefore, investigation in this area could be very helpful for future therapy of cancer. This review gives detail information on the role of PARP in DNA damage repair, the role of PARP inhibitors and chemistry of currently available PARP inhibitors.

scholarly journals DNA Damage/Repair Management in Cancers

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1050 ◽  
Author(s):  
Jehad F. Alhmoud ◽  
John F. Woolley ◽  
Ala-Eddin Al Moustafa ◽  
Mohammed Imad Malki
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dna Damage Repair ◽  
Critical Factor ◽  
Dna Lesions ◽  
Cancer Development ◽  
Dna Damaging Agents ◽  
Damage Repair ◽  
Repair Mechanisms ◽  
Dna Strand

DNA damage is well recognized as a critical factor in cancer development and progression. DNA lesions create an abnormal nucleotide or nucleotide fragment, causing a break in one or both chains of the DNA strand. When DNA damage occurs, the possibility of generated mutations increases. Genomic instability is one of the most important factors that lead to cancer development. DNA repair pathways perform the essential role of correcting the DNA lesions that occur from DNA damaging agents or carcinogens, thus maintaining genomic stability. Inefficient DNA repair is a critical driving force behind cancer establishment, progression and evolution. A thorough understanding of DNA repair mechanisms in cancer will allow for better therapeutic intervention. In this review we will discuss the relationship between DNA damage/repair mechanisms and cancer, and how we can target these pathways.

scholarly journals The roles of RNA in DNA double-strand break repair

2020 ◽  
Vol 122 (5) ◽  
pp. 613-623 ◽  
Author(s):  
Aldo S. Bader ◽  
Ben R. Hawley ◽  
Ania Wilczynska ◽  
Martin Bushell
Keyword(s):  
Dna Repair ◽  
Cancer Progression ◽  
Genome Stability ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Critical Role ◽  
Strand Break ◽  
Rna Molecules ◽  
Repair Mechanisms ◽  
Recent Developments

AbstractEffective DNA repair is essential for cell survival: a failure to correctly repair damage leads to the accumulation of mutations and is the driving force for carcinogenesis. Multiple pathways have evolved to protect against both intrinsic and extrinsic genotoxic events, and recent developments have highlighted an unforeseen critical role for RNA in ensuring genome stability. It is currently unclear exactly how RNA molecules participate in the repair pathways, although many models have been proposed and it is possible that RNA acts in diverse ways to facilitate DNA repair. A number of well-documented DNA repair factors have been described to have RNA-binding capacities and, moreover, screens investigating DNA-damage repair mechanisms have identified RNA-binding proteins as a major group of novel factors involved in DNA repair. In this review, we integrate some of these datasets to identify commonalities that might highlight novel and interesting factors for future investigations. This emerging role for RNA opens up a new dimension in the field of DNA repair; we discuss its impact on our current understanding of DNA repair processes and consider how it might influence cancer progression.

scholarly journals DNA repair system defects - role in oncogenesis and cancer therapy

2014 ◽  
Vol 95 (3) ◽  
pp. 307-314
Author(s):  
S V Boychuk ◽  
B R Ramazanov
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Cancer Therapy ◽  
Single Case ◽  
Published Data ◽  
Repair System ◽  
Damage Repair ◽  
Anti Cancer ◽  
Repair Mechanisms ◽  
Acquired Abnormalities

Inherited and acquired abnormalities in DNA damage repair system may lead to cancer and other diseases, as well as to act as one of the key factors determining the patient’s responsiveness to chemo- and radiotherapy. Nowadays, the principles of the personalized therapy, based on specific features of disease development and pathogenesis of a solitary organism or in a small group, are applied to treat a broad number of diseases, including cancers. This approach allows to choose the most effective cancer therapy in every single case of cancer, based on the genetic analysis and expression level of specific proteins. One of the promising approaches for increasing the effectiveness of non-surgical cancer treatments - to develop the methods to increase the cancer cells sensitivity to conducted chemotherapy, based on using the DNA repair system defects for the better anti-cancer effect. The review covers some types of DNA repair system defects occurring while chemo- and radiotherapy. Perspectives of the possible influences on DNA repair mechanisms treated as possible targets for both anti-cancer treatment and for increasing the effects of cancer chemo- and radiotherapy, are discussed in the review considering the available published data and results of own research. DNA repair system defects play an important role in cancer genesis, but as well can determine the good response of patients with such defects to chemo- and radiotherapy (inducing different types of DNA damage).

Post-translational modifications of lysine in DNA-damage repair

2012 ◽  
Vol 52 ◽  
pp. 93-111 ◽  
Author(s):  
Snehajyoti Chatterjee ◽  
Parijat Senapati ◽  
Tapas K. Kundu
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Post Translational Modifications ◽  
Dna Repair Mechanisms ◽  
The Past ◽  
Damage Repair ◽  
Lysine Residues ◽  
Repair Mechanisms ◽  
Genotoxic Insult

DNA damage in cells is often the result of constant genotoxic insult. Nevertheless, efficient DNA repair pathways are able to maintain genomic integrity. Over the past decade it has been revealed that it is not only kinase signalling pathways which play a central role in this process, but also the different post-translational modifications at lysine residues of histone (chromatin) and non-histone proteins. These lysine modifications include acetylation, methylation, ubiquitination and SUMOylation. Genomic instability is often the major cause of different diseases, especially cancer, where lysine modifications are altered and thereby have an impact on the various DNA repair mechanisms. This chapter will discuss the recent advances in our understanding of the role of different lysine modifications in DNA repair and its physiological consequences.

scholarly journals DNA Damage Repair in Brain Tumor Immunotherapy

2022 ◽  
Vol 12 ◽  
Author(s):  
Shihong Zhao ◽  
Boya Xu ◽  
Wenbin Ma ◽  
Hao Chen ◽  
Chuanlu Jiang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Brain Tumors ◽  
Dna Damage Repair ◽  
Tumor Development ◽  
Clinical Work ◽  
Repair Process ◽  
Damage Repair ◽  
Rational Combination ◽  
Repair Mechanisms ◽  
Harsh Conditions

With the gradual understanding of tumor development, many tumor therapies have been invented and applied in clinical work, and immunotherapy has been widely concerned as an emerging hot topic in the last decade. It is worth noting that immunotherapy is nowadays applied under too harsh conditions, and many tumors are defined as “cold tumors” that are not sensitive to immunotherapy, and brain tumors are typical of them. However, there is much evidence that suggests a link between DNA damage repair mechanisms and immunotherapy. This may be a breakthrough for the application of immunotherapy in brain tumors. Therefore, in this review, first, we will describe the common pathways of DNA damage repair. Second, we will focus on immunotherapy and analyze the mechanisms of DNA damage repair involved in the immune process. Third, we will review biomarkers that have been or may be used to evaluate immunotherapy for brain tumors, such as TAMs, RPA, and other molecules that may provide a precursor assessment for the rational implementation of immunotherapy for brain tumors. Finally, we will discuss the rational combination of immunotherapy with other therapeutic approaches that have an impact on the DNA damage repair process in order to open new pathways for the application of immunotherapy in brain tumors, to maximize the effect of immunotherapy on DNA damage repair mechanisms, and to provide ideas and guidance for immunotherapy in brain tumors.

scholarly journals Deep Sequencing Discovery and Profiling of Known and Novel miRNAs Produced in Response to DNA Damage in Rice

2021 ◽  
Vol 22 (18) ◽  
pp. 9958
Author(s):  
Jianxiang Zhang ◽  
Cheng Xu ◽  
Kangwei Liu ◽  
Yaoqinq Li ◽  
Mengna Wang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Gene Transcription ◽  
Target Genes ◽  
Expression Patterns ◽  
Dna Damage Repair ◽  
Repair Process ◽  
Differentially Expressed ◽  
Damage Repair ◽  
Differentially Expressed Mirnas

Under extreme environmental conditions such as ultraviolet and ionizing radiation, plants may suffer DNA damage. If these damages are not repaired accurately and rapidly, they may lead to chromosomal abnormalities or even cell death. Therefore, organisms have evolved various DNA repair mechanisms to cope with DNA damage which include gene transcription and post-translational regulation. MicroRNA (miRNA) is a type of non-coding single-stranded RNA molecule encoded by endogenous genes. They can promote DNA damage repair by regulating target gene transcription. Here, roots from seedlings of the japonica rice cultivar ‘Yandao 8’ that were treated with bleomycin were collected for transcriptome-level sequencing, using non-treated roots as controls. A total of 14,716,232 and 17,369,981 reads mapping to miRNAs were identified in bleomycin-treated and control groups, respectively, including 513 known and 72 novel miRNAs. Compared with the control group, 150 miRNAs showed differential expression levels. Target predictions of these differentially expressed miRNAs yielded 8731 potential gene targets. KEGG annotation and a gene ontology analysis indicated that the highest-ranked target genes were classified into metabolic processes, RNA degradation, DNA repair, and so on. Notably, the DNA repair process was significantly enriched in both analyses. Among these differentially expressed miRNAs, 58 miRNAs and 41 corresponding potential target genes were predicted to be related to DNA repair. RT-qPCR results confirmed that the expression patterns of 20 selected miRNAs were similar to those from the sequencing results, whereas four miRNAs gave opposite results. The opposing expression patterns of several miRNAs with regards to their target genes relating to the DNA repair process were also validated by RT-qPCR. These findings provide valuable information for further functional studies of miRNA involvement in DNA damage repair in rice.

scholarly journals Quantitatively profiling acetylome of DNA repair proteins in early DNA damage

2020 ◽  
Author(s):  
Shiqin Li ◽  
Lin Zhou ◽  
Xinli Liu ◽  
Bingbing Shi ◽  
Tingting Huang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Protein Function ◽  
Critical Role ◽  
Repair Process ◽  
Post Translational Modification ◽  
Affinity Enrichment ◽  
Dna Repair Proteins ◽  
Liquid Chromatography Tandem Mass ◽  
And Function

Abstract Background：Lysine acetylation is a reversible regulated post-translational modification that can regulate the stability, localization, and function of proteins in multiple cellular processes. However, the regulative mechanism of acetylation on the repair proteins in the early DNA damage is not fully understood. Methods：We performed a global proteome and acetylome of DNA repair proteins in DNA damage in 1 h after treated with epirubicin by using high affinity enrichment and high-resolution liquid chromatography–tandem mass spectrometry approaches. Results: 190 Kac sites in 50 repair proteins were identified in cells treated with epirubicin as compared to the control. 42 acetylated lysine sites and 24 deacetylated lysine sites were observed in 21 and 16 repair proteins, respectively. 7 repair proteins simultaneously contained both acetylated and deacetylated lysine sites. 11 acetylation sites were located in the function domains of 7 repair proteins that might reveal mechanisms by which acetylations alter DDR protein function. In 17 repair proteins, the induced acetylation changes were for the first time identified in the present study. Conclusion: The proteome and acetylome results indicated that fast acetylation or deacetylation on these repair proteins might play a critical role in the early DNA damage repair process.

scholarly journals Platinum Complexes in Colorectal Cancer and Other Solid Tumors

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2073
Author(s):  
Beate Köberle ◽  
Sarah Schoch
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Dna Repair ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Platinum Complexes ◽  
Dna Lesions ◽  
Dna Damage Signaling ◽  
Repair Mechanisms ◽  
P53 Inactivation

Cisplatin is one of the most commonly used drugs for the treatment of various solid neoplasms, including testicular, lung, ovarian, head and neck, and bladder cancers. Unfortunately, the therapeutic efficacy of cisplatin against colorectal cancer is poor. Various mechanisms appear to contribute to cisplatin resistance in cancer cells, including reduced drug accumulation, enhanced drug detoxification, modulation of DNA repair mechanisms, and finally alterations in cisplatin DNA damage signaling preventing apoptosis in cancer cells. Regarding colorectal cancer, defects in mismatch repair and altered p53-mediated DNA damage signaling are the main factors controlling the resistance phenotype. In particular, p53 inactivation appears to be associated with chemoresistance and poor prognosis. To overcome resistance in cancers, several strategies can be envisaged. Improved cisplatin analogues, which retain activity in resistant cancer, might be applied. Targeting p53-mediated DNA damage signaling provides another therapeutic strategy to circumvent cisplatin resistance. This review provides an overview on the DNA repair pathways involved in the processing of cisplatin damage and will describe signal transduction from cisplatin DNA lesions, with special attention given to colorectal cancer cells. Furthermore, examples for improved platinum compounds and biochemical modulators of cisplatin DNA damage signaling will be presented in the context of colon cancer therapy.

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.

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