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https://www.readbyqxmd.com/read/29775409/transactivation-domain-of-p53-regulates-dna-repair-and-integrity-in-human-ips-cells
#1
Ramaswamy Kannappan, Saidulu Mattapally, Pooja A Wagle, Jianyi Zhang
The role of p53 transactivation domain (p53-TAD), a multifunctional and dynamic domain, on DNA repair and retaining DNA integrity in human iPS cells has never been studied. p53-TAD was knocked out in iPS cells using CRISPR/Cas9 and was confirmed by DNA sequencing. p53-TAD KO cells were characterized by: accelerated proliferation, decreased population doubling time, and unaltered Bcl2, BBC3, IGF1R, Bax and altered Mdm2, p21, and PIDD transcripts expression. In p53-TAD KO cells p53 regulated DNA repair proteins XPA, DNA polH and DDB2 expression were found to be reduced compared to p53-WT cells...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29741662/physical-and-functional-interplay-between-pcna-dna-clamp-and-mre11-rad50-complex-from-the-archaeon-pyrococcus-furiosus
#2
Gaëlle Hogrel, Yang Lu, Sébastien Laurent, Etienne Henry, Clarisse Etienne, Duy Khanh Phung, Rémi Dulermo, Audrey Bossé, Pierre-François Pluchon, Béatrice Clouet-d'Orval, Didier Flament
Several archaeal species prevalent in extreme environments are particularly exposed to factors likely to cause DNA damages. These include hyperthermophilic archaea (HA), living at temperatures >70°C, which arguably have efficient strategies and robust genome guardians to repair DNA damage threatening their genome integrity. In contrast to Eukarya and other archaea, homologous recombination appears to be a vital pathway in HA, and the Mre11-Rad50 complex exerts a broad influence on the initiation of this DNA damage response process...
May 8, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29727754/genomic-instability-in-adult-men-involved-in-processing-electronic-waste-in-northern-china
#3
Yan Wang, Xiaohui Sun, Lianying Fang, Keqiu Li, Ping Yang, Liqing Du, Kaihua Ji, Jinhan Wang, Qiang Liu, Chang Xu, Guang Li, John P Giesy, Markus Hecker
BACKGROUND: Managing and recycling electronic waste (e-waste), while useful and necessary, has resulted in significant contamination of several environments in China. The area around Tianjin, China has become one of the world's largest e-waste disposal centers, where electronics are processed by manually disassembly or burning, which can result in serious exposure of workers to a multitude of toxicants. OBJECTIVE: The present study assessed potential genomic damage in workers involved in recycling e-waste...
May 1, 2018: Environment International
https://www.readbyqxmd.com/read/29726012/rad50-germline-mutations-are-associated-with-poor-survival-in-brca1-2-negative-breast-cancer-patients
#4
Cong Fan, Juan Zhang, Tao Ouyang, Jinfeng Li, Tianfeng Wang, Zhaoqing Fan, Tie Fan, Benyao Lin, Yuntao Xie
RAD50 is a highly conserved DNA double-strand break (DSB) repair gene. However, the associations between RAD50 germline mutations and the survival and risk of breast cancer have not been fully elucidated. Here, we aimed to investigate the clinical impact of RAD50 germline mutations in a large cohort of unselected breast cancer patients. In this study, RAD50 germline mutations were determined using next-generation sequencing in 7657 consecutive unselected breast cancer patients without BRCA1/2 mutations. We also screened for RAD50 recurrent mutations (L719fs, K994fs, and H1269fs) in 5000 healthy controls using Sanger sequencing...
May 4, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29712888/regulation-of-dna-damage-repair-and-lipid-uptake-by-cx-3-cr1-in-epithelial-ovarian-carcinoma
#5
Jia Xie, Hilal Gurler Main, Joelle D Sacks, Goda G Muralidhar, Maria V Barbolina
Failure of currently used cytotoxic chemotherapy is one of the main reasons behind high mortality from metastatic high grade serous ovarian carcinoma. We found that high expression of a receptor for fractalkine (CX3 CR1) significantly correlated with shorter survival of patients with serous ovarian carcinoma treated with cytotoxic DNA damage chemotherapies, and reduction of CX3 CR1 expression resulted in sensitization to several DNA damaging modalities, including x-ray radiation and cisplatin. Here, we show that CX3 CR1 plays a role in double-strand DNA break response and repair by regulating expression of RAD50 by a MYC-dependent mechanism...
May 1, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29709199/the-mre11-rad50-nbs1-complex-conducts-the-orchestration-of-damage-signaling-and-outcomes-to-stress-in-dna-replication-and-repair
#6
Aleem Syed, John A Tainer
Genomic instability in disease and its fidelity in health depend on the DNA damage response (DDR), regulated in part from the complex of meiotic recombination 11 homolog 1 (MRE11), ATP-binding cassette-ATPase (RAD50), and phosphopeptide-binding Nijmegen breakage syndrome protein 1 (NBS1). The MRE11-RAD50-NBS1 (MRN) complex forms a multifunctional DDR machine. Within its network assemblies, MRN is the core conductor for the initial and sustained responses to DNA double-strand breaks, stalled replication forks, dysfunctional telomeres, and viral DNA infection...
April 25, 2018: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/29705126/the-mre11a470t-mutation-and-homeologous-interactions-increase-error-prone-bir
#7
In-Joon Baek, Courtney Parke, Arthur J Lustig
In the absence of the RNA-templated reverse transcriptase, telomerase, the predominant means of terminal addition, arises from break-induced replication (BIR) at multiple homologous subtelomeric Y' loci and among internal homeologous (imperfect) (polyG1-3T) tracts. These last tracts are interspersed between subtelomeric Y' direct repeats. One major survivor class contains very short (~50 bp) terminal telomere repeats. This size is sufficient for slow growth and partial telomere functionality and cell viability...
April 26, 2018: Gene
https://www.readbyqxmd.com/read/29686104/interdependent-and-separable-functions-of-caenorhabditis-elegans-mrn-c-complex-members-couple-formation-and-repair-of-meiotic-dsbs
#8
Chloe Girard, Baptiste Roelens, Karl A Zawadzki, Anne M Villeneuve
Faithful inheritance of genetic information through sexual reproduction relies on the formation of crossovers between homologous chromosomes during meiosis, which, in turn, relies on the formation and repair of numerous double-strand breaks (DSBs). As DSBs pose a potential threat to the genome, mechanisms that ensure timely and error-free DSB repair are crucial for successful meiosis. Here, we identify NBS-1, the Caenorhabditis elegans ortholog of the NBS1 (mutated in Nijmegen Breakage Syndrome) subunit of the conserved MRE11-RAD50-NBS1/Xrs2 (MRN) complex, as a key mediator of DSB repair via homologous recombination (HR) during meiosis...
April 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29661984/unrepaired-dna-damage-in-macrophages-causes-elevation-of-particulate-matter-induced-airway-inflammatory-response
#9
Man Luo, Zhengqiang Bao, Feng Xu, Xiaohui Wang, Fei Li, Wen Li, Zhihua Chen, Songmin Ying, Huahao Shen
The inflammatory cascade can be initiated with the recognition of damaged DNA. Macrophages play an essential role in particulate matter (PM)-induced airway inflammation. In this study, we aim to explore the PM induced DNA damage response of macrophages and its function in airway inflammation. The DNA damage response and inflammatory response were assessed using bone marrow-derived macrophages following PM treatment and mouse model instilled intratracheally with PM. We found that PM induced significant DNA damage both in vitro and in vivo and simultaneously triggered a rapid DNA damage response, represented by nuclear RPA, 53BP1 and γH2AX foci formation...
April 14, 2018: Aging
https://www.readbyqxmd.com/read/29547809/serotype-specific-restriction-of-wild-type-adenoviruses-by-the-cellular-mre11-rad50-nbs1-complex
#10
Neha J Pancholi, Matthew D Weitzman
During viral replication in the nucleus, the DNA genomes of adenoviruses are accessible to cellular DNA-binding proteins. Human adenovirus type 5 (Ad5) targets the cellular Mre11-Rad50-Nbs1 complex (MRN) to evade detection by the DNA damage response (DDR). Ad5 mutants that cannot target MRN have reduced viral propagation. Previous studies showed that diverse adenovirus serotypes interact differently with MRN. While these studies revealed diverse MRN interactions among serotypes, it remains unclear how these differences influence viral replication...
March 13, 2018: Virology
https://www.readbyqxmd.com/read/29545967/egfr-tyrosine-kinase-inhibitor-hs-10182-increases-radiation-sensitivity-in-non-small-cell-lung-cancers-with-egfr-t790m-mutation
#11
Yang Chen, Youyou Wang, Lujun Zhao, Ping Wang, Jifeng Sun, Rudi Bao, Chenghai Li, Ningbo Liu
Objective: To investigate the potential of HS-10182, a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), as a radiosensitizer in non-small cell lung cancer (NSCLC). Methods: Two cell lines of NSCLCs, A549 that possesses wild-type (WT) EGFRs and H1975 that possesses EGFR L858R/T790M double mutations, were treated with HS-10182 at various concentrations, and cell viabilities were determined using the MTS assay. The cells were tested by clonogenic survival assays to identify the radiosensitivity of both groups...
February 2018: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/29524880/isoorientin-triggers-apoptosis-of-hepatoblastoma-by-inducing-dna-double-strand-breaks-and-suppressing-homologous-recombination-repair
#12
Dehong Huang, Lei Jin, Zhengkang Li, Ji Wu, Ni Zhang, Dianrong Zhou, Xiaorong Ni, Tieying Hou
Hepatoblastoma (HB) is the most common malignant liver tumor in children. DNA and DNA-associated processes are one of the most important targets of chemotherapeutic agents. Isoorientin (Iso), a natural flavonoid compound, can be extracted from several plant species. The effects of Iso and its molecular mechanisms on hepatic malignancies remain unclear. Herein, the anti-tumor effects of Iso in HB and its underlying mechanisms were explored. We found that Iso significantly inhibited the proliferation of HB cells both in vitro and in vivo...
May 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29514136/deficiency-in-dna-damage-response-of-enterocytes-accelerates-intestinal-stem-cell-aging-in-drosophila
#13
Joung-Sun Park, Ho-Jun Jeon, Jung-Hoon Pyo, Young-Shin Kim, Mi-Ae Yoo
Stem cell dysfunction is closely linked to tissue and organismal aging and age-related diseases, and heavily influenced by the niche cells' environment. The DNA damage response (DDR) is a key pathway for tissue degeneration and organismal aging; however, the precise protective role of DDR in stem cell/niche aging is unclear. The Drosophila midgut is an excellent model to study the biology of stem cell/niche aging because of its easy genetic manipulation and its short lifespan. Here, we showed that deficiency of DDR in Drosophila enterocytes (ECs) accelerates intestinal stem cell (ISC) aging...
March 7, 2018: Aging
https://www.readbyqxmd.com/read/29488113/the-sulfolobus-solfataricus-recq-like-dna-helicase-hel112-inhibits-the-nura-hera-complex-exonuclease-activity
#14
Mariarosaria De Falco, Federica Massa, Mosè Rossi, Mariarita De Felice
ATPase/Helicases and nucleases play important roles in DNA end-resection, a critical step during homologous recombination repair in all organisms. In hyperthermophilic archaea the exo-endonuclease NurA and the ATPase HerA cooperate with the highly conserved Mre11-Rad50 complex in 3' single-stranded DNA (ssDNA) end processing to coordinate repair of double-stranded DNA breaks. Little is known, however, about the assembly mechanism and activation of the HerA-NurA complex. In this study we demonstrate that the NurA exonuclease activity is inhibited by the Sulfolobus solfataricus RecQ-like Hel112 helicase...
February 27, 2018: Extremophiles: Life Under Extreme Conditions
https://www.readbyqxmd.com/read/29466740/talen-induced-double-strand-break-repair-of-ctg-trinucleotide-repeats
#15
Valentine Mosbach, Lucie Poggi, David Viterbo, Marine Charpentier, Guy-Franck Richard
Trinucleotide repeat expansions involving CTG/CAG triplets are responsible for several neurodegenerative disorders, including myotonic dystrophy and Huntington's disease. Because expansions trigger the disease, contracting repeat length could be a possible approach to gene therapy for these disorders. Here, we show that a TALEN-induced double-strand break was very efficient at contracting expanded CTG repeats in yeast. We show that RAD51, POL32, and DNL4 are dispensable for double-strand break repair within CTG repeats, the only required genes being RAD50, SAE2, and RAD52...
February 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29458776/methods-to-study-dna-end-resection-ii-biochemical-reconstitution-assays
#16
Cosimo Pinto, Roopesh Anand, Petr Cejka
DNA end resection initiates the largely accurate repair of DNA double-strand breaks (DSBs) by homologous recombination. Specifically, recombination requires the formation of 3' overhangs at DSB sites, which is carried out by nucleases that specifically degrade 5'-terminated DNA. In most cases, DNA end resection is a two-step process, comprising of initial short-range followed by more processive long-range resection. In this chapter, we describe selected assays that reconstitute both the short- and long-range pathways...
2018: Methods in Enzymology
https://www.readbyqxmd.com/read/29458761/methods-to-study-dna-end-resection-i-recombinant-protein-purification
#17
Roopesh Anand, Cosimo Pinto, Petr Cejka
Accurate repair of DNA double-strand breaks (DSBs) is carried out by homologous recombination. In order to repair DNA breaks by the recombination pathway, the 5'-terminated DNA strand at DSB sites must be first nucleolytically processed to produce 3'-overhang. The process is termed DNA end resection and involves the interplay of several nuclease complexes. DNA end resection commits DSB repair to the recombination pathway including a process termed single-strand annealing, as resected DNA ends are generally nonligatable by the competing nonhomologous end-joining machinery...
2018: Methods in Enzymology
https://www.readbyqxmd.com/read/29458756/kinetic-analysis-of-the-exonuclease-activity-of-the-bacteriophage-t4-mre11-rad50-complex
#18
Tibebe A Teklemariam, Osvaldo D Rivera, Scott W Nelson
Bacteriophage T4 encodes orthologs of the proteins Rad50 (gp46) and Mre11 (gp47), which form a heterotetrameric complex (MR) that is responsible for host genome degradation and the processing of DNA ends for recombination-dependent DNA repair. In this chapter, we describe the ensemble methods currently employed by our laboratory to characterize the exonuclease activity of the T4 MR complex. DNA exonucleases play a vital role in maintaining the integrity of DNA through their participation in DNA repair pathways and as proofreaders for DNA polymerases...
2018: Methods in Enzymology
https://www.readbyqxmd.com/read/29450116/the-potential-of-the-newly-isolated-thermotolerant-kluyveromyces-marxianus-for-high-temperature-ethanol-production-using-sweet-sorghum-juice
#19
Warayutt Pilap, Sudarat Thanonkeo, Preekamol Klanrit, Pornthap Thanonkeo
In this work, the newly isolated thermotolerant Kluyveromyces marxianus DBKKUY-103 exhibited a high ethanol fermentation efficiency at high temperatures using sweet sorghum juice (SSJ). The highest ethanol concentrations and productivities achieved under the optimum conditions using thermotolerant K. marxianus DBKKUY-103 were 85.16 g/l and 1.42 g/l.h at 37 °C and 83.46 g/l and 1.39 g/l.h at 40 °C, respectively. The expression levels of genes during ethanol fermentation at 40 °C were evaluated and the results found that the transcriptional levels of the RAD10 , RAD14 , RAD33 , RAD50 , ATPH , ATP4 , ATP16 , and ATP20 genes were up-regulated compared with those at 30 °C, suggesting that the high growth and high ethanol production efficiencies of K...
February 2018: 3 Biotech
https://www.readbyqxmd.com/read/29445421/evidence-for-a-pre-malignant-cell-line-in-a-skin-biopsy-from-a-patient-with-nijmegen-breakage-syndrome
#20
Raneem Habib, Heidemarie Neitzel, Aurelie Ernst, John K L Wong, Bozenna Goryluk-Kozakiewicz, Antje Gerlach, Ilja Demuth, Karl Sperling, Krystyna Chrzanowska
Background: Nijmegen breakage syndrome is an autosomal recessive disorder characterized by microcephaly, immunodeficiency, hypersensitivity to X-irradiation, and a high predisposition to cancer. Nibrin, the product of the NBN gene, is part of the MRE11/RAD50 (MRN) complex that is involved in the repair of DNA double strand breaks (DSBs), and plays a critical role in the processing of DSBs in immune gene rearrangements, telomere maintenance, and meiotic recombination. NBS skin fibroblasts grow slowly in culture and enter early into senescence...
2018: Molecular Cytogenetics
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