Role of Rad51 and DNA repair in cancer: A molecular perspective

Publication date: Available online 27 January 2020Source: Pharmacology &TherapeuticsAuthor(s): Erik Laurini, Domenico Marson, Alice Fermeglia, Suzana Aulic, Maurizio Fermeglia, Sabrina PriclAbstractThe maintenance of genome integrity is essential for any organism survival and for the inheritance of traits to offspring. To the purpose, cells have developed a complex DNA repair system to defend the genetic information against both endogenous and exogenous sources of damage. Accordingly, multiple repair pathways can be aroused from the diverse forms of DNA lesions, which can be effective per se or via crosstalk with others to complete the whole DNA repair process. Deficiencies in DNA healing resulting in faulty repair and/or prolonged DNA damage can lead to genes mutations, chromosome rearrangements, genomic instability, and finally carcinogenesis and/or cancer progression. Although it might seem paradoxical, at the same time such defects in DNA repair pathways may have therapeutic implications for potential clinical practice. Here we provide an overview of the main DNA repair pathways, with special focus on the role played by homologous repair and the RAD51 recombinase protein in the cellular DNA damage response. We next discuss the recombinase structure and function per se and in combination with all its principal mediators and regulators. Finally, we conclude with an analysis of the manifold roles that RAD51 plays in carcinogenesis, cancer progression and anticancer drug ...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research

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Publication date: 18 February 2020Source: Cell Reports, Volume 30, Issue 7Author(s): Mu-Yan Cai, Connor E. Dunn, Wenxu Chen, Bose S. Kochupurakkal, Huy Nguyen, Lisa A. Moreau, Geoffrey I. Shapiro, Kalindi Parmar, David Kozono, Alan D. D’AndreaSummaryCells deficient in ataxia telangiectasia mutated (ATM) are hypersensitive to ionizing radiation and other anti-cancer agents that induce double-strand DNA breaks. ATM inhibitors may therefore sensitize cancer cells to these agents. Some cancers may also have underlying genetic defects predisposing them to an ATM inhibitor monotherapy response. We have conducted a genome-w...
Source: Cell Reports - Category: Cytology Source Type: research
el Moss Arginine-specific mono-adenosine diphosphate (ADP)-ribosylation is a nicotinamide adenine dinucleotide (NAD)+-dependent, reversible post-translational modification involving the transfer of an ADP-ribose from NAD+ by bacterial toxins and eukaryotic ADP-ribosyltransferases (ARTs) to arginine on an acceptor protein or peptide. ADP-ribosylarginine hydrolase 1 (ARH1) catalyzes the cleavage of the ADP-ribose-arginine bond, regenerating (arginine)protein. Arginine-specific mono-ADP-ribosylation catalyzed by bacterial toxins was first identified as a mechanism of disease pathogenesis. Cholera toxin ADP-ribosylates and...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
M. Wells Amir Abdollahi Radiation-induced normal tissue toxicity often limits the curative treatment of cancer. Moreover, normal tissue relative biological effectiveness data for high-linear energy transfer particles are urgently needed. We propose a strategy based on transcriptome analysis of patient-derived human intestinal organoids (HIO) to determine molecular surrogates for radioresponse of gastrointestinal (GI) organs at risk in a personalized manner. HIO were generated from induced pluripotent stem cells (iPSC), which were derived from skin biopsies of three patients, including two patients with FANCA deficie...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Dikomey Wittig Arenz The PI3K/Akt/mTOR pathway is frequently altered in human papillomavirus (HPV)-positive and negative squamous cell carcinoma of the head and neck (HNSCC) and overstimulation is associated with poor prognosis. PI3K drives Akt activation and constitutive signaling acts pro-proliferative, supports cell survival, DNA repair, and contributes to radioresistance. Since the small molecule NVP-BEZ235 (BEZ235) is a potent dual inhibitor of this pathway, we were interested whether BEZ235 could be an efficient radiosensitizer. The 50 nM BEZ235 was found to abrogate endogenous and irradiation-induced pho...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
ConclusionCNDAG-induced double-strand breaks are repaired mainly through homologous recombination.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
midt With roles in DNA repair, recombination, replication and transcription, members of the RecQ DNA helicase family maintain genome integrity from bacteria to mammals. Mutations in human RecQ helicases BLM, WRN and RecQL4 cause incurable disorders characterized by genome instability, increased cancer predisposition and premature adult-onset aging. Yeast cells lacking the RecQ helicase Sgs1 share many of the cellular defects of human cells lacking BLM, including hypersensitivity to DNA damaging agents and replication stress, shortened lifespan, genome instability and mitotic hyper-recombination, making them invaluable ...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Review Source Type: research
This is the latest in a series of yearly posts in which I suggest areas of development for biotech startups I'd like to see actively developed as a part of the longevity industry in the near future. Today, this year, is a good time to be starting a company focused on the production of a novel therapeutic approach to intervening in the aging process. There is a great deal of funding for seed stage investment, and many compelling projects lacking champions, yet to be carried forward from academia into preclinical development. Numerous scientific and industry crossover conferences are now held every year, at which it is possi...
Source: Fight Aging! - Category: Research Authors: Tags: Investment Source Type: blogs
AbstractPurpose of ReviewConventional and novel applications of Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi) are reviewed in the context of recently published clinical trials and preclinical data supporting rapidly expanding uses of this class of chemotherapy.Recent FindingsPARPi block a pathway of DNA repair and target defects in homologous recombination repair (HRR), a pathway responsible for high-fidelity repair of double-strand breaks in DNA. BRCA1/2 proteins are essential to this pathway. Approximately 15 –30% of women with ovarian cancer will have a germline or somaticBRCA mutat...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research
Discussion of the Evolutionary Genetics of Aging Thymic Involution Contributes to Immunosenescence and Inflammaging The Potential for Exosome Therapies to Treat Sarcopenia Correlations of Mitochondrial DNA Copy Number and Epigenetic Age Measures Evidence for PASK Deficiency to Reduce the Impact of Aging in Mice The Aging Retina, a Mirror of the Aging Brain Evidence for Loss of Capillary Density to be Important in Heart Disease Aspects of Immune System Aging Proceed More Rapidly in Men Deacetylation of the NLRP3 Inflammasome as a Way to Control Chronic Inflammation Transplantation of Senescent Cells is an ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusions: Our findings demonstrate that Regorafenib enhanced radiosensitivity of breast cancer cells by inhibiting the expression of multiple receptor tyrosine kinases, VEGF-mediated angiogenesis and DNA damage response in TNBC. Therefore, combining Regorafenib with radiation and antiangiogenic agents will be beneficial and effective in controlling TNBC. PMID: 32052681 [PubMed - as supplied by publisher]
Source: International Journal of Radiation Biology - Category: Radiology Tags: Int J Radiat Biol Source Type: research
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