scholarly journals Radio-Resistance and DNA Repair in Pediatric Diffuse Midline Gliomas

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2813
Author(s):  
Henriette Pedersen ◽  
Kjeld Schmiegelow ◽  
Petra Hamerlik
Keyword(s):  
Recent Literature ◽  
Malignant Gliomas ◽  
Therapeutic Interventions ◽  
Damage Response ◽  
Histone H3k27 ◽  
Current Therapies ◽  
Nonsurgical Therapy ◽  
Synthetically Lethal ◽  
Dna Damage Response Pathway ◽  
H3k27m Mutation

Malignant gliomas (MG) are among the most prevalent and lethal primary intrinsic brain tumors. Although radiotherapy (RT) is the most effective nonsurgical therapy, recurrence is universal. Dysregulated DNA damage response pathway (DDR) signaling, rampant genomic instability, and radio-resistance are among the hallmarks of MGs, with current therapies only offering palliation. A subgroup of pediatric high-grade gliomas (pHGG) is characterized by H3K27M mutation, which drives global loss of di- and trimethylation of histone H3K27. Here, we review the most recent literature and discuss the key studies dissecting the molecular biology of H3K27M-mutated gliomas in children. We speculate that the aberrant activation and/or deactivation of some of the key components of DDR may be synthetically lethal to H3K27M mutation and thus can open novel avenues for effective therapeutic interventions for patients suffering from this deadly disease.

scholarly journals New Potential Biomarkers for Chronic Kidney Disease Management—A Review of the Literature

2020 ◽  
Vol 22 (1) ◽  
pp. 43
Author(s):  
Irina Lousa ◽  
Flávio Reis ◽  
Idalina Beirão ◽  
Rui Alves ◽  
Luís Belo ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Practice ◽  
Kidney Disease ◽  
Renal Damage ◽  
Recent Literature ◽  
Therapeutic Interventions ◽  
Review Of The Literature ◽  
Medical Need ◽  
Early Use ◽  
Reasonable Approach

The prevalence of chronic kidney disease (CKD) is increasing worldwide, and the mortality rate continues to be unacceptably high. The biomarkers currently used in clinical practice are considered relevant when there is already significant renal impairment compromising the early use of potentially successful therapeutic interventions. More sensitive and specific biomarkers to detect CKD earlier on and improve patients’ prognoses are an important unmet medical need. The aim of this review is to summarize the recent literature on new promising early CKD biomarkers of renal function, tubular lesions, endothelial dysfunction and inflammation, and on the auspicious findings from metabolomic studies in this field. Most of the studied biomarkers require further validation in large studies and in a broad range of populations in order to be implemented into routine CKD management. A panel of biomarkers, including earlier biomarkers of renal damage, seems to be a reasonable approach to be applied in clinical practice to allow earlier diagnosis and better disease characterization based on the underlying etiologic process.

scholarly journals DNA Damage Response Pathway and Replication Fork Stress During Oligonucleotide Directed Gene Editing

2012 ◽  
Vol 1 ◽  
pp. e18 ◽  
Author(s):  
Melissa Bonner ◽  
Bryan Strouse ◽  
Mindy Applegate ◽  
Paula Livingston ◽  
Eric B Kmiec
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Replication Fork ◽  
Gene Editing ◽  
Damage Response ◽  
Dna Damage Response Pathway

scholarly journals Structural basis of γH2AX recognition by human PTIP BRCT5-BRCT6 domains in the DNA damage response pathway

FEBS Letters ◽  
2011 ◽  
Vol 585 (24) ◽  
pp. 3874-3879 ◽  
Author(s):  
Wei Yan ◽  
Zhenhua Shao ◽  
Fudong Li ◽  
Liwen Niu ◽  
Yunyu Shi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Structural Basis ◽  
Damage Response ◽  
Dna Damage Response Pathway

scholarly journals RTT109 AND Fun30 proteins mediate epigenetic regulation of the DNA damage response pathway in C. albicans

2021 ◽  
Author(s):  
Prashant Kumar Maurya ◽  
Pramita Garai ◽  
Kaveri Goel ◽  
Himanshu Bhatt ◽  
Aarti Goyal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Regulation Of Gene Expression ◽  
Repair Pathway ◽  
Fungal Cell ◽  
Opportunistic Fungi ◽  
Damage Response ◽  
H3 Acetylation ◽  
Dna Damage Response Pathway

Fun30, an ATP-dependent chromatin remodeller, from S. cerevisiae mediates both regulation of gene expression as well as DNA damage response/repair. In this paper, we have characterized the biochemical and physiological function of Fun30 from the opportunistic fungi, C. albicans. Biochemically, the protein shows DNA-stimulated ATPase activity. Physiologically, the protein co-regulates transcription of RTT109, TEL1, MEC1, and SNF2-genes that encode for proteins involved in DNA damage response and repair pathway. The expression of FUN30, in turn, is regulated by histone H3 acetylation catalysed by Rtt109 encoded by RTT109. The RTT109Hz/FUN30Hz mutant strain shows sensitivity to oxidative stress and resistance to MMS as compared to the wild type strain. Quantitative PCR showed that the sensitivity to oxidative stress results from downregulation of MEC1, RAD9, MRC1 and RAD5 expression; ChIP experiments showed Fun30 but not H3ac regulates the expression of these genes in response to oxidative stress. In contrast, on treatment with MMS, the expression of RAD9 is upregulated and this upregulation is co-regulated by both Fun30 and H3 acetylation catalysed by Rtt109. Thus, Fun30 and H3 acetylation mediate the response of the fungal cell to genotoxic agents in C. albicans by regulating the expression of DNA damage response and repair pathway genes.

Modeling chemotherapy-induced stress to identify rational combination therapies in the DNA damage response pathway

2018 ◽  
Vol 11 (540) ◽  
pp. eaat0229 ◽  
Author(s):  
Ozan Alkan ◽  
Birgit Schoeberl ◽  
Millie Shah ◽  
Alexander Koshkaryev ◽  
Tim Heinemann ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Combination Therapies ◽  
Induced Stress ◽  
Damage Response ◽  
Rational Combination ◽  
Dna Damage Response Pathway

scholarly journals APE2 promotes DNA damage response pathway from a single-strand break

2018 ◽  
Vol 46 (5) ◽  
pp. 2479-2494 ◽  
Author(s):  
Yunfeng Lin ◽  
Liping Bai ◽  
Steven Cupello ◽  
Md Akram Hossain ◽  
Bradley Deem ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Strand Break ◽  
Single Strand ◽  
Single Strand Break ◽  
Damage Response ◽  
Dna Damage Response Pathway

Improving Prospects for Targeting RAS

2015 ◽  
Vol 33 (31) ◽  
pp. 3650-3659 ◽  
Author(s):  
Harshabad Singh ◽  
Dan L. Longo ◽  
Bruce A. Chabner
Keyword(s):  
Clinical Trials ◽  
Structure Function ◽  
Solid Tumors ◽  
Therapeutic Interventions ◽  
Ras Proteins ◽  
Ras Mutations ◽  
Downstream Signaling ◽  
Synthetically Lethal ◽  
Intense Research ◽  
Ras Inhibitors

RAS mutations are among the most common oncogenic drivers in human cancers, affecting nearly a third of all solid tumors and around a fifth of common myeloid malignancies, but they have evaded therapeutic interventions, despite being the focus of intense research over the last three decades. Recent discoveries lend new understanding about the structure, function, and signaling of RAS and have opened new avenues for development of much needed new therapies. We discuss the various approaches under investigation to target mutant RAS proteins. The recent development of direct RAS inhibitors specific to KRAS G12C mutations represents a landmark discovery that promises to change the perception about RAS's druggability. Multiple clinical trials targeting synthetically lethal partners and/or downstream signaling partners of RAS are underway. Novel inhibitors targeting various arms of RAS processing and signaling have yielded encouraging results in the laboratory, but refinement of the drug-like properties of these molecules is required before they will be ready for the clinic.

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