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DNA DAMAGE AND REPAIR

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https://www.readbyqxmd.com/read/29161272/global-transcriptome-profile-reveals-abundance-of-dna-damage-response-and-repair-genes-in-individuals-from-high-level-natural-radiation-areas-of-kerala-coast
#1
Vinay Jain, Birajalaxmi Das
The high level natural radiation areas (HLNRA) of Kerala coast in south west India is unique for its wide variation in the background radiation dose (<1.0mGy to 45mGy/year) and vast population size. Several biological studies conducted in this area did not reveal any adverse effects of chronic low dose and low dose rate radiation on human population. In the present study, global transcriptome analysis was carried out in peripheral blood mono-nuclear cells of 36 individuals belonging to different background dose groups [NLNRA, (Group I, ≤1...
2017: PloS One
https://www.readbyqxmd.com/read/29159324/dna-repair-after-oxidative-stress-current-challenges
#2
Bennett Van Houten, Gloria A Santa-Gonzalez, Mauricio Camargo
Reactive oxygen and nitrogen species damage cellular macromolecules including DNA. Cells have a robust base excision repair pathway to deal with this damage in both nuclear and mitochondrial genomes. However, mitochondria lack nucleotide excision repair. Evidence suggests that chronic oxidative stress can induce protective pathways lowering genotoxicity. Understanding oxidant injury to DNA and its repair is critical for our understanding the pathophysiology of a wide range of human disorders.
February 2018: Current Opinion in Toxicology
https://www.readbyqxmd.com/read/29158484/the-hsf1-parp13-parp1-complex-facilitates-dna-repair-and-promotes-mammary-tumorigenesis
#3
Mitsuaki Fujimoto, Ryosuke Takii, Eiichi Takaki, Arpit Katiyar, Ryuichiro Nakato, Katsuhiko Shirahige, Akira Nakai
Poly(ADP-ribose) polymerase 1 (PARP1) is involved in DNA repair, chromatin structure, and transcription. However, the mechanisms that regulate PARP1 distribution on DNA are poorly understood. Here, we show that heat shock transcription factor 1 (HSF1) recruits PARP1 through the scaffold protein PARP13. In response to DNA damage, activated and auto-poly-ADP-ribosylated PARP1 dissociates from HSF1-PARP13, and redistributes to DNA lesions and DNA damage-inducible gene loci. Histone deacetylase 1 maintains PARP1 in the ternary complex by inactivating PARP1 through deacetylation...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29158426/cohesin-function-in-cohesion-condensation-and-dna-repair-is-regulated-by-wpl1p-via-a-common-mechanism-in-saccharomyces%C3%A2-cerevisiae
#4
Michelle S Bloom, Douglas Koshland, Vincent Guacci
Cohesin tethers DNA to mediate sister chromatid cohesion, chromosome condensation, and DNA repair. How the cell regulates cohesin to perform these distinct functions remains to be elucidated. One cohesin regulator, Wpl1p, was characterized in Saccharomyces cerevisiae as a promoter of efficient cohesion and an inhibitor of condensation. Wpl1p is also required for resistance to DNA damaging agents. Here we provide evidence that Wpl1p promotes the timely repair of DNA damage induced during S-phase. Previous studies indicate that Wpl1p destabilizes cohesin's binding to DNA by modulating the interface between the cohesin subunits Mcd1p and Smc3p...
November 20, 2017: Genetics
https://www.readbyqxmd.com/read/29157966/antibiotic-killing-through-incomplete-dna-repair
#5
Benno H Ter Kuile, Marloes Hoeksema
Two recent studies show that incomplete repair of DNA damage due to oxidized nucleotides is crucial for reactive oxygen species (ROS)-related antimicrobial lethality. Using widely different experimental approaches they both reach the same conclusions on the role of downstream ROS production in cell killing upon exposure to bactericidal antimicrobials.
November 17, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/29157749/mithramycin-a-enhances-tumor-sensitivity-to-mitotic-catastrophe-resulting-from-dna-damage
#6
Bradley T Scroggins, Jeffrey Burkeen, Ayla O White, Eun Joo Chung, Darmood Wei, Su I Chung, Luca F Valle, Shilpa S Patil, Grace McKay-Corkum, Kathryn E Hudak, W Marston Linehan, Deborah E Citrin
PURPOSE: Specificity protein 1 (SP1) is involved in the transcription of several genes implicated in tumor maintenance. We investigated the effects of mithramycin A (MTA), an inhibitor of SP1 DNA binding, on radiation response. METHODS AND MATERIALS: Clonogenic survival after irradiation was assessed in 2 tumor cell lines (A549, UM-UC-3) and 1 human fibroblast line (BJ) after SP1 knockdown or MTA treatment. DNA damage repair was evaluated using γH2AX foci formation, and mitotic catastrophe was assessed using nuclear morphology...
October 12, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29157089/the-relationship-between-dna-single-stranded-damage-response-and-double-stranded-damage-response
#7
Aiqing Ma, Xianhua Dai
The damage response of DNA single-stranded breaks(SSBs) and double-stranded breaks(DSBs) are two relatively independent processes involving different signaling pathways and protein factors, but there are still many overlapping parts. All of them can activate p53 protein, then the activated p53 regulates the damage response of single-stranded breaks or double-stranded breaks in transcriptional regulation and non-transcriptional regulation. Especially, the two types of damage would compete for RPA and ATR resources in damage repair process...
November 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29156909/genetic-biomarkers-associated-with-response-to-palliative-radiotherapy-in-patients-with-painful-bone-metastases
#8
Anthony Furfari, Bo Angela Wan, Keyue Ding, Andrew Wong, Liting Zhu, Andrea Bezjak, Rebecca Wong, Carolyn F Wilson, Carlo DeAngelis, Azar Azad, Edward Chow, George S Charames
BACKGROUND: Palliative radiotherapy (RT) is effective in patients with painful bone metastases. Genetic factors may identify subgroup of patients who responded to RT. To identify DNA biomarkers associated with response to palliative RT. METHODS: Patients who received a single 8 Gy dose of RT for painful bone metastases were categorised into responders (n=36), non-responders (NR) (n=71). Saliva samples were sequenced to identify single-nucleotide variants (SNVs) in genes with known disease-causing variants from inflammation, radiation response, and DNA damage pathways...
October 10, 2017: Annals of Palliative Medicine
https://www.readbyqxmd.com/read/29156796/downregulation-of-dna-repair-proteins-and-increased-dna-damage-in-hypoxic-colon-cancer-cells-is-a-therapeutically-exploitable-vulnerability
#9
Jennifer M J Jongen, Lizet M van der Waals, Kari Trumpi, Jamila Laoukili, Niek A Peters, Susanne J Schenning-van Schelven, Klaas M Govaert, Inne H M Borel Rinkes, Onno Kranenburg
Surgical removal of colorectal cancer (CRC) liver metastases generates areas of tissue hypoxia. Hypoxia imposes a stem-like phenotype on residual tumor cells and promotes tumor recurrence. Moreover, in primary CRC, gene expression signatures reflecting hypoxia and a stem-like phenotype are highly expressed in the aggressive Consensus Molecular Subtype 4 (CMS4). Therapeutic strategies eliminating hypoxic stem-like cells may limit recurrence following resection of primary tumors or metastases. Here we show that expression of DNA repair genes is strongly suppressed in CMS4 and inversely correlated with hypoxia-inducible factor-1 alpha (HIF1α) and HIF-2α co-expression signatures...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156764/the-neil1-g83d-germline-dna-glycosylase-variant-induces-genomic-instability-and-cellular-transformation
#10
Heather A Galick, Carolyn G Marsden, Scott Kathe, Julie A Dragon, Lindsay Volk, Antonia A Nemec, Susan S Wallace, Aishwarya Prakash, Sylvie Doublié, Joann B Sweasy
Base excision repair (BER) is a key genome maintenance pathway. The NEIL1 DNA glycosylase recognizes oxidized bases, and likely removes damage in advance of the replication fork. The rs5745906 SNP of the NEIL1 gene is a rare human germline variant that encodes the NEIL1 G83D protein, which is devoid of DNA glycosylase activity. Here we show that expression of G83D NEIL1 in MCF10A immortalized but non-transformed mammary epithelial cells leads to replication fork stress. Upon treatment with hydrogen peroxide, we observe increased levels of stalled replication forks in cells expressing G83D NEIL1 versus cells expressing the wild-type (WT) protein...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156754/functional-characterization-of-a-novel-transcript-of-ercc1-in-chemotherapy-resistance-of-ovarian-cancer
#11
Jia Liu, Lin Zhang, Ping Mao, Guoqiang Jiang, Likun Liu, Jing Wang, Wei Yang, Lawrence Owusu, Weiling Li
Approximately 15-20% of ovarian cancer patients receiving platinum-based chemotherapy are primary platinum-resistant. Identification of these patients and transfer to other more effective therapy could reduce the morbidity of ovarian cancer. ERCC1 is a DNA repair gene which can complex with XPF to repair cisplatin-induced DNA damage and cause chemotherapy resistance. In this study, we found a novel ERCC1 transcript initiated upstream of the normal transcription initiation site. The expression of this larger ERCC1 transcript dramatically increased following cisplatin treatment in ovarian cancer cells and was regulated by the MAPK pathway...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156695/mir-2964a-5p-binding-site-snp-regulates-atm-expression-contributing-to-age-related-cataract-risk
#12
Han Rong, Shanshan Gu, Guowei Zhang, Lihua Kang, Mei Yang, Junfang Zhang, Xinyue Shen, Huaijin Guan
This study was to explore the involvement of DNA repair genes in the pathogenesis of age-related cataract (ARC). We genotyped nine single nucleotide polymorphisms (SNPs) of genes responsible to DNA double strand breaks (DSBs) in 804 ARC cases and 804 controls in a cohort of eye diseases in Chinese population and found that the ataxia telangiectasia mutated (ATM) gene-rs4585:G>T was significantly associated with ARC risk. An in vitro functional test found that miR-2964a-5p specifically down-regulated luciferase reporter expression and ATM expression in the cell lines transfected with rs4585 T allele compared to rs4585 G allele...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156686/crosstalk-between-mismatch-repair-and-base-excision-repair-in-human-gastric-cancer
#13
Valeria Simonelli, Giuseppe Leuzzi, Giorgia Basile, Mariarosaria D'Errico, Paola Fortini, Annapaola Franchitto, Valentina Viti, Ashley R Brown, Eleonora Parlanti, Barbara Pascucci, Domenico Palli, Alessandro Giuliani, Fabio Palombo, Robert W Sobol, Eugenia Dogliotti
DNA repair gene expression in a set of gastric cancers suggested an inverse association between the expression of the mismatch repair (MMR) gene MLH1 and that of the base excision repair (BER) gene DNA polymerase β (Polβ). To gain insight into possible crosstalk of these two repair pathways in cancer, we analysed human gastric adenocarcinoma AGS cells over-expressing Polβ or Polβ active site mutants, alone or in combination with MLH1 silencing. Next, we investigated the cellular response to the alkylating agent methyl methanesulfonate (MMS) and the purine analogue 6-thioguanine (6-TG), agents that induce lesions that are substrates for BER and/or MMR...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156421/impaired-mitochondrial-respiration-in-human-carotid-plaque-atherosclerosis-a-potential-role-for-pink1-in-vascular-smooth-muscle-cell-energetics
#14
Craig K Docherty, Andy Carswell, Elaine Friel, John R Mercer
BACKGROUND AND AIMS: DNA damage and mitochondrial dysfunction are thought to play an essential role in ageing and the energetic decline of vascular smooth muscle cells (VSMCs) essential for maintaining plaque integrity. We aimed to better understand VSMCs and identify potentially useful compensatory pathways that could extend their lifespan. Moreover, we wanted to assess if defects in mitochondrial respiration exist in human atherosclerotic plaques and to identify the appropriate markers that may reflect a switch in VSMC energy metabolism...
November 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29155820/mass-spectrometry-based-quantification-of-the-cellular-response-to-ultraviolet-radiation-in-hela-cells
#15
Hong Xu, Xuanyi Chen, Nanjiao Ying, Meixia Wang, Xiaoli Xu, Rongyi Shi, Yuejin Hua
Ultraviolet (UV) irradiation is a common form of DNA damage that can cause pyrimidine dimers between DNA, which can cause gene mutations, even double-strand breaks and threaten genome stability. If DNA repair systems default their roles at this stage, the organism can be damaged and result in disease, especially cancer. To better understand the cellular response to this form of damage, we applied highly sensitive mass spectrometry to perform comparative proteomics of phosphorylation in HeLa cells. A total of 4367 phosphorylation sites in 2100 proteins were identified, many of which had not been reported previously...
2017: PloS One
https://www.readbyqxmd.com/read/29155761/advanced-confocal-microscopy-techniques-to-study-protein-protein-interactions-and-kinetics-at-dna-lesions
#16
Soňa Legartová, Jana Suchánková, Jana Krejčí, Alena Kovaříková, Eva Bártová
Local microirradiation with lasers represents a useful tool for studies of DNA-repair-related processes in live cells. Here, we describe a methodological approach to analyzing protein kinetics at DNA lesions over time or protein-protein interactions on locally microirradiated chromatin. We also show how to recognize individual phases of the cell cycle using the Fucci cellular system to study cell-cycle-dependent protein kinetics at DNA lesions. A methodological description of the use of two UV lasers (355 nm and 405 nm) to induce different types of DNA damage is also presented...
November 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155171/manganese-chloride-induces-histone-acetylation-changes-in-neuronal-cells-its-role-in-manganese-induced-damage
#17
Zhenkun Guo, Zhipeng Zhang, Qingqing Wang, Jie Zhang, Lijin Wang, Qunwei Zhang, Huangyuan Li, Siying Wu
Manganese neurotoxicity presents with Parkinson-like symptoms, with degeneration of dopaminergic neurons in the basal ganglia as the principal pathological feature. Manganese neurotoxicity studies may contribute to a better understanding of the mechanism of Parkinson's disease. Here, we examined the effects of manganese on histone acetylation, a major epigenetic change in chromatin that can regulate gene expression, chromatin remodelling, cell cycle progression, DNA repair and apoptosis. In this study, we found that manganese chloride (MnCl2) may significantly suppress the acetylation of histone H3 and H4 in PC12 cells and SHSY5Y cells in a time-dependent manner...
November 16, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/29155057/effects-of-different-hypoxia-degrees-on-endothelial-cell-cultures-time-course-study
#18
Ioana Baldea, Ioana Teacoe, Diana Elena Olteanu, Cristina Vaida-Voievod, Andra Clichici, Alexandru Sirbu, Gabriela Adriana Filip, Simona Clichici
INTRODUCTION: Exposure of the endothelial cells to hypoxia, the decrease in oxygen supply can trigger an endothelial response. This response is involved in inflammatory diseases, tumorigenesis, and also with the micro vascular damage associated with aging. The aim of our study was to determine the hypoxia/re-oxygenation induced response in vitro, using human umbilical vein endothelial cells (HUVEC) cultures, at different time points with focus on cell viability, apoptosis oxidative stress and angiogenesis stimulation...
November 15, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29154141/novel-genes-associated-with-amyotrophic-lateral-sclerosis-diagnostic-and-clinical-implications
#19
REVIEW
Ruth Chia, Adriano Chiò, Bryan J Traynor
BACKGROUND: The disease course of amyotrophic lateral sclerosis (ALS) is rapid and, because its pathophysiology is unclear, few effective treatments are available. Genetic research aims to understand the underlying mechanisms of ALS and identify potential therapeutic targets. The first gene associated with ALS was SOD1, identified in 1993 and, by early 2014, more than 20 genes had been identified as causative of, or highly associated with, ALS. These genetic discoveries have identified key disease pathways that are therapeutically testable and could potentially lead to the development of better treatments for people with ALS...
November 16, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/29154038/dna-damage-and-neurodegenerative-phenotypes-in-aged-ciz1-null-mice
#20
Mohammad Moshahid Khan, Jianfeng Xiao, Damini Patel, Mark S LeDoux
Cell-cycle dysfunction and faulty DNA repair are closely intertwined pathobiological processes that may contribute to several neurodegenerative disorders. CDKN1A interacting zinc finger protein 1 (CIZ1) plays a critical role in DNA replication and cell-cycle progression at the G1/S checkpoint. Germline or somatic variants in CIZ1 have been linked to several neural and extra-neural diseases. Recently, we showed that germline knockout of Ciz1 is associated with motor and hematological abnormalities in young adult mice...
November 16, 2017: Neurobiology of Aging
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