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DNA damage repair

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https://www.readbyqxmd.com/read/27925687/dna-base-excision-repair-proteins-ape-1-and-xrcc-1-are-overexpressed-in-oral-tongue-squamous-cell-carcinoma
#1
Thalita Santana, Melka Coêlho Sá, Edilmar de Moura Santos, Hébel Cavalcanti Galvão, Ricardo D Coletta, Roseana de Almeida Freitas
BACKGROUND: DNA repair systems play a critical role in protecting the human genome from damage caused by carcinogens. Modifications in DNA repair genes may be responsible for tumor development and resistance of malignant cells to chemotherapeutic agents. The major pathway for oxidative DNA damage repair is the base excision repair pathway. This study aimed to assess the immunoexpression of DNA repair proteins APE-1 and XRCC-1 and its association with clinical, histological and survival parameters in oral tongue squamous cell carcinoma in order to investigate a possible role for those proteins in tumor behavior...
December 7, 2016: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/27925473/the-role-of-cancer-stem-cells-in-tumor-heterogeneity-and-resistance-to-therapy
#2
Christina Valbirk Konrad, Reshma Murali, Binitha Anu Varghese, Radhika Nair
Cancer is a heterogenous disease displaying marked inter- and intra-tumoral diversity. The existence of cancer stem cells (CSCs) has been experimentally demonstrated in a number of cancer types as a subpopulation of tumor cells that drives the tumorigenic and metastatic properties of the entire cancer. Thus, eradication of the CSC population is critical for the complete ablation of a tumor. This is, however, confounded by the inherent resistance of CSCs to standard anticancer therapies, eventually leading to the outgrowth of resistant tumor cells and relapse in patients...
September 3, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27925276/conformational-and-intermolecular-interaction-dynamics-of-photolyase-cryptochrome-proteins-monitored-by-the-time-resolved-diffusion-technique
#3
Masato Kondoh, Masahide Terazima
Cryptochrome (CRY), a blue light sensor protein, possesses a similar domain structure to photolyase (PHR) that, upon absorption of light, repairs DNA damage. In this review, we compare the reaction dynamics of these systems by monitoring the reaction kinetics of conformation change and intermolecular interaction change based on time-dependent diffusion coefficient measurements obtained by using the pulsed laser-induced transient grating technique. Using this method, time-dependent biomolecular interactions, such as transient dissociation reactions in solution, have been successfully detected in real time...
December 7, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27924031/ubiquitylation-dependent-regulation-of-neil1-by-mule-and-trim26-is-required-for-the-cellular-dna-damage-response
#4
Matthew J Edmonds, Rachel J Carter, Catherine M Nickson, Sarah C Williams, Jason L Parsons
Endonuclease VIII-like protein 1 (NEIL1) is a DNA glycosylase involved in initiating the base excision repair pathway, the major cellular mechanism for repairing DNA base damage. Here, we have purified the major E3 ubiquitin ligases from human cells responsible for regulation of NEIL1 by ubiquitylation. Interestingly, we have identified two enzymes that catalyse NEIL1 polyubiquitylation, Mcl-1 ubiquitin ligase E3 (Mule) and tripartite motif 26 (TRIM26). We demonstrate that these enzymes are capable of polyubiquitylating NEIL1 in vitro, and that both catalyse ubiquitylation of NEIL1 within the same C-terminal lysine residues...
October 18, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27924011/roles-for-aprin-pds5b-in-homologous-recombination-and-in-ovarian-cancer-prediction
#5
Anthony M Couturier, Hubert Fleury, Anne-Marie Patenaude, Victoria L Bentley, Amélie Rodrigue, Yan Coulombe, Joshi Niraj, Joris Pauty, Jason N Berman, Graham Dellaire, Javier M Di Noia, Anne-Marie Mes-Masson, Jean-Yves Masson
APRIN (PDS5 cohesin associated factor B) interacts with both the cohesin complex and the BRCA2 tumor suppressor. How APRIN influences cohesion and DNA repair processes is not well understood. Here, we show that APRIN is recruited to DNA damage sites. We find that APRIN interacts directly with RAD51, PALB2 and BRCA2. APRIN stimulates RAD51-mediated DNA strand invasion. APRIN also binds DNA with an affinity for D-loop structures and single-strand (ss) DNA. APRIN is a new homologous recombination (HR) mediator as it counteracts the RPA inhibitory effect on RAD51 loading to ssDNA...
October 24, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27924001/histone-chaperone-activity-of-arabidopsis-thaliana-nrp1-is-blocked-by-cytochrome-c
#6
Katiuska González-Arzola, Antonio Díaz-Quintana, Francisco Rivero-Rodríguez, Adrián Velázquez-Campoy, Miguel A De la Rosa, Irene Díaz-Moreno
Higher-order plants and mammals use similar mechanisms to repair and tolerate oxidative DNA damage. Most studies on the DNA repair process have focused on yeast and mammals, in which histone chaperone-mediated nucleosome disassembly/reassembly is essential for DNA to be accessible to repair machinery. However, little is known about the specific role and modulation of histone chaperones in the context of DNA damage in plants. Here, the histone chaperone NRP1, which is closely related to human SET/TAF-Iβ, was found to exhibit nucleosome assembly activity in vitro and to accumulate in the chromatin of Arabidopsis thaliana after DNA breaks...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923681/evaluation-of-dna-damaging-potential-of-bisphenol-a-and-its-selected-analogs-in-human-peripheral-blood-mononuclear-cells-in-vitro-study
#7
Katarzyna Mokra, Agnieszka Kuźmińska-Surowaniec, Katarzyna Woźniak, Jaromir Michałowicz
In the present study, we have investigated DNA-damaging potential of BPA and its analogs, i.e. bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF) in human peripheral blood mononuclear cells (PBMCs) using the alkaline and neutral versions of the comet assay, which allowed to evaluate DNA single strand-breaks (SSBs) and double strandbreaks (DSBs). The use of the alkaline version of comet assay made also possible to analyze the kinetics of DNA repair in PBMCs after exposure of the cells to BPA or its analogs...
December 3, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27923671/a-core-component-of-the-cul4-ubiquitin-ligase-complexes-ddb1-regulates-spermatogenesis-in-the-chinese-mitten-crab-eriocheir-sinensis
#8
AnYu Fang, XueJie Li, YuanLi Wang, DiYue Pan, Qun Wang
Studies in mammals have shown that damaged DNA-binding protein 1 (DDB1) is a multifunctional protein that recognizes UV-induced DNA lesions and activates nucleotide excision repair process, and could also be a linker protein for Cullin4 in ubiquitination to regulate cell cycle progression. However, there are few studies of DBB1 in crustaceans. In this study, a cDNA representing the DDB1 gene from Eriocheir sinensis (Es-DDB1) was cloned successfully. The full length Es-DDB1 cDNA comprises 4871 nucleotides, and encodes an open-reading frame (ORF) of 1137 amino acid residues...
December 3, 2016: Gene
https://www.readbyqxmd.com/read/27923055/a-novel-rrm3-function-in-restricting-dna-replication-via-an-orc5-binding-domain-is-genetically-separable-from-rrm3-function-as-an-atpase-helicase-in-facilitating-fork-progression
#9
Salahuddin Syed, Claus Desler, Lene J Rasmussen, Kristina H Schmidt
In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186-212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27922819/early-age-decline-in-dna-repair-capacity-in-the-liver-in-depth-profile-of-differential-gene-expression
#10
Avital Guedj, Anat Geiger-Maor, Eithan Galun, Hagai Amsalem, Jacob Rachmilewitz
Aging is associated with progressive decline in cell function and with increased damage to macromolecular components. DNA damage, in the form of double-strand breaks (DSBs), increases with age and in turn, contributes to the aging process and age-related diseases. DNA strand breaks triggers a set of highly orchestrated signaling events known as the DNA damage response (DDR), which coordinates DNA repair. However, whether the accumulation of DNA damage with age is a result of decreased repair capacity, remains to be determined...
November 30, 2016: Aging
https://www.readbyqxmd.com/read/27920426/crystal-structure-based-discovery-of-a-novel-synthesized-parp1-inhibitor-ol-1-with-apoptosis-inducing-mechanisms-in-triple-negative-breast-cancer
#11
Leilei Fu, Shuya Wang, Xuan Wang, Peiqi Wang, Yaxin Zheng, Dahong Yao, Mingrui Guo, Lan Zhang, Liang Ouyang
Poly (ADP-ribose) polymerase-1 (PARP1) is a highly conserved enzyme focused on the self-repair of cellular DNA damage. Until now, numbers of PARP inhibitors have been reported and used for breast cancer therapy in recent years, especially in TNBC. However, developing a new type PARP inhibitor with distinctive skeleton is alternatively promising strategy for TNBC therapy. In this study, based on co-crystallization studies and pharmacophore-docking-based virtual screening, we discovered a series of dihydrodibenzo[b,e]-oxepin compounds as PARP1 inhibitors...
December 2016: Scientific Reports
https://www.readbyqxmd.com/read/27919340/consequences-of-irradiation-on-adult-spermatogenesis-between-infertility-and-hereditary-risk
#12
Henri-Baptiste Marjault, Isabelle Allemand
DNA damage response in adult spermatogenic cells should limit the propagation of mutations to the offspring, without being detrimental to fertility. In differentiating spermatogenic cells, the genomic instability is limited in time, whereas in spermatogonial stem cells it can be maintained all along life. Spermatogonial stem cells are long-lived cells that support normal germ cell differentiation and must be preserved throughout life. However after irradiation spermatogenesis recovery can be impaired as a consequence of the radiation-induced decline in spermatogonial stem cell...
October 2016: Mutation Research
https://www.readbyqxmd.com/read/27917193/dna-damage-response-and-autophagy-a-meaningful-partnership
#13
REVIEW
Aristides G Eliopoulos, Sophia Havaki, Vassilis G Gorgoulis
Autophagy and the DNA damage response (DDR) are biological processes essential for cellular and organismal homeostasis. Herein, we summarize and discuss emerging evidence linking DDR to autophagy. We highlight published data suggesting that autophagy is activated by DNA damage and is required for several functional outcomes of DDR signaling, including repair of DNA lesions, senescence, cell death, and cytokine secretion. Uncovering the mechanisms by which autophagy and DDR are intertwined provides novel insight into the pathobiology of conditions associated with accumulation of DNA damage, including cancer and aging, and novel concepts for the development of improved therapeutic strategies against these pathologies...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27915381/regulation-of-non-homologous-end-joining-via-post-translational-modifications-of-components-of-the-ligation-step
#14
REVIEW
Kristína Durdíková, Miroslav Chovanec
DNA double-strand breaks are the most serious type of DNA damage and non-homologous end joining (NHEJ) is an important pathway for their repair. In Saccharomyces cerevisiae, three complexes mediate the canonical NHEJ pathway, Ku (Ku70/Ku80), MRX (Mre11/Rad50/Xrs2) and DNA ligase IV (Dnl4/Lif1). Mammalian NHEJ is more complex, primarily as a consequence of the fact that more factors are involved in the process, and also because higher chromatin organization and more complex regulatory networks exist in mammals...
December 3, 2016: Current Genetics
https://www.readbyqxmd.com/read/27915231/predominant-role-of-dna-polymerase-eta-and-p53-dependent-translesion-synthesis-in-the-survival-of-ultraviolet-irradiated-human-cells
#15
Leticia K Lerner, Guilherme Francisco, Daniela T Soltys, Clarissa R R Rocha, Annabel Quinet, Alexandre T Vessoni, Ligia P Castro, Taynah I P David, Silvina O Bustos, Bryan E Strauss, Vanesa Gottifredi, Anne Stary, Alain Sarasin, Roger Chammas, Carlos F M Menck
Genome lesions trigger biological responses that help cells manage damaged DNA, improving cell survival. Pol eta is a translesion synthesis (TLS) polymerase that bypasses lesions that block replicative polymerases, avoiding continued stalling of replication forks, which could lead to cell death. p53 also plays an important role in preventing cell death after ultraviolet (UV) light exposure. Intriguingly, we show that p53 does so by favoring translesion DNA synthesis by pol eta. In fact, the p53-dependent induction of pol eta in normal and DNA repair-deficient XP-C human cells after UV exposure has a protective effect on cell survival after challenging UV exposures, which was absent in p53- and Pol H-silenced cells...
December 2, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27915139/impairment-of-fetal-hematopoietic-stem-cell-function-in-the-absence-of-fancd2
#16
Sakiko Suzuki, Ronny R Racine, Nathan A Manalo, Sharon B Cantor, Glen D Raffel
Fanconi Anemia (FA), results from mutations in genes necessary for DNA damage repair and often leads to progressive bone marrow failure. Although the exhaustion of the bone marrow leads to cytopenias in FA patients as they age, evidence from human FA and mouse model fetal livers suggests hematopoietic defects originate in utero which may lead to deficient seeding of the bone marrow. To address this possibility, we examined the consequences of loss of Fancd2, a central component of the FA pathway. Examination of E14...
November 30, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27915046/dna-damage-related-crosstalk-between-the-nucleus-and-mitochondria
#17
Mohammad Saki, Aishwarya Prakash
The electron transport chain is the primary pathway by which a cell generates energy in the form of ATP. Byproducts of this process produce reactive oxygen species that can cause damage to mitochondrial DNA. If not properly repaired, the accumulation of DNA damage can lead to mitochondrial dysfunction linked to several human disorders including neurodegenerative diseases and cancer. Mitochondria are able to combat oxidative DNA damage via repair mechanisms that are analogous to those found in the nucleus. Of the repair pathways currently reported in the mitochondria, the base excision repair pathway is the most comprehensively described...
November 30, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27914352/searching-for-novel-modes-of-toxic-actions-of-oil-spill-using-e-%C3%A2-coli-live-cell-array-reporter-system-a-hebei-spirit-oil-spill-study
#18
Dawoon Jung, Miao Guan, Sangwoo Lee, Cheolmin Kim, Hyesoo Shin, Seongjin Hong, Un Hyuk Yim, Won Joon Shim, John P Giesy, Jong Seong Khim, Xiaowei Zhang, Kyungho Choi
Oil is a complex mixture of numerous compounds. Therefore, oil spills near shore can cause various adverse effects on coastal ecosystems. However, most toxicological assessments conducted on oil spill sites have focused on limited modes of toxic actions. In the present study, we utilized the Escherichia coli (E. coli) live cell array system (LCA) to identify novel modes of toxicities of the oil spill-affected sediments. For this purpose, sediment samples were collected from an area heavily polluted by Hebei Spirit oil spill (HSOS) incident of 2007...
November 30, 2016: Chemosphere
https://www.readbyqxmd.com/read/27914347/differential-crosstalk-between-global-dna-methylation-and-metabolomics-associated-with-cell-type-specific-stress-response-by-pristine-and-functionalized-mwcnt
#19
Nivedita Chatterjee, Jisu Yang, Dahye Yoon, Suhkmann Kim, Sang-Woo Joo, Jinhee Choi
The present study endeavored to evaluate the comprehensive mechanisms of MWCNT-induced toxicity with particular emphasis on understanding cell specificity in relation to surface functionalization of MWCNT. Following treatment with differentially functionalized (hydroxylation/carboxylation) MWCNT on human bronchial epithelial (BEAS-2B) and human hepatoma (HepG2) cell lines, intracellular uptake, various toxicological end points, global metabolomics profiling and DNA methylation were evaluated. Herein, the comparative in vitro studies ascertained that surface functionalization diminished the toxic potentiality of MWCNT in respect of their pristine counterpart...
November 9, 2016: Biomaterials
https://www.readbyqxmd.com/read/27911399/tools-to-study-the-role-of-architectural-protein-hmgb1-in-the-processing-of-helix-distorting-site-specific-dna-interstrand-crosslinks
#20
Anirban Mukherjee, Karen M Vasquez
High mobility group box 1 (HMGB1) protein is a non-histone architectural protein that is involved in regulating many important functions in the genome, such as transcription, DNA replication, and DNA repair. HMGB1 binds to structurally distorted DNA with higher affinity than to canonical B-DNA. For example, we found that HMGB1 binds to DNA interstrand crosslinks (ICLs), which covalently link the two strands of the DNA, cause distortion of the helix, and if left unrepaired can cause cell death. Due to their cytotoxic potential, several ICL-inducing agents are currently used as chemotherapeutic agents in the clinic...
November 10, 2016: Journal of Visualized Experiments: JoVE
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