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https://www.readbyqxmd.com/read/29233683/caspase-mediated-cleavage-of-x-ray-repair-cross-complementing-group-4-promotes-apoptosis-by-enhancing-nuclear-translocation-of-caspase-activated-dnase
#1
Yumi Sunatani, Radhika Pankaj Kamdar, Mukesh Kumar Sharma, Tadashi Matsui, Ryo Sakasai, Mitsumasa Hashimoto, Yasuhito Ishigaki, Yoshihisa Matsumoto, Kuniyoshi Iwabuchi
X-ray repair cross-complementing group 4 (XRCC4), a repair protein for DNA double-strand breaks, is cleaved by caspases during apoptosis. In this study, we examined the role of XRCC4 in apoptosis. Cell lines, derived from XRCC4-deficient M10 mouse lymphoma cells and stably expressing wild-type XRCC4 or caspase-resistant XRCC4, were established and treated with staurosporine (STS) to induce apoptosis. In STS-induced apoptosis, expression of wild-type, but not caspase-resistant, XRCC4 in XRCC4-deficient cells enhanced oligonucleosomal DNA fragmentation and the appearance of TUNEL-positive cells by promoting nuclear translocation of caspase-activated DNase (CAD), a major nuclease for oligonucleosomal DNA fragmentation...
December 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29152133/prognostic-significance-of-xrcc4-expression-in-hepatocellular-carcinoma
#2
Jun Lu, Xing-Zhizi Wang, Tian-Qi Zhang, Xiao-Ying Huang, Jin-Guang Yao, Chao Wang, Zhong-Hong Wei, Yun Ma, Xue-Min Wu, Chun-Ying Luo, Qiang Xia, Xi-Dai Long
Background: Our previous investigations have shown that the variants of X-ray repair complementing 4 (XRCC4) may be involved in hepatocellular carcinoma (hepatocarcinoma) tumorigenesis. This study aimed to investigate the possible prognostic significance of XRCC4 expression for hepatocarcinoma patients and possible value for the selection of transarterial chemoembolization (TACE) treatment. Materials and Methods: We conducted a hospital-based retrospective analysis (including 421 hepatocarcinoma cases) to analyze the effects of XRCC4 on hepatocarcinoma prognosis and TACE...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29144403/the-non-homologous-end-joining-protein-paxx-acts-to-restrict-hsv-1-infection
#3
Ben J Trigg, Katharina B Lauer, Paula Fernandes Dos Santos, Heather Coleman, Gabriel Balmus, Daniel S Mansur, Brian J Ferguson
Herpes simplex virus 1 (HSV-1) has extensive interactions with the host DNA damage response (DDR) machinery that can be either detrimental or beneficial to the virus. Proteins in the homologous recombination pathway are known to be required for efficient replication of the viral genome, while different members of the classical non-homologous end-joining (c-NHEJ) pathway have opposing effects on HSV-1 infection. Here, we have investigated the role of the recently-discovered c-NHEJ component, PAXX (Paralogue of XRCC4 and XLF), which we found to be excluded from the nucleus during HSV-1 infection...
November 16, 2017: Viruses
https://www.readbyqxmd.com/read/29077092/paxx-and-xlf-interplay-revealed-by-impaired-cns-development-and-immunodeficiency-of-double-ko-mice
#4
Vincent Abramowski, Olivier Etienne, Ramy Elsaid, Junjie Yang, Aurélie Berland, Laetitia Kermasson, Benoit Roch, Stefania Musilli, Jean-Paul Moussu, Karelia Lipson-Ruffert, Patrick Revy, Ana Cumano, François D Boussin, Jean-Pierre de Villartay
The repair of DNA double-stranded breaks (DNAdsb) through non-homologous end joining (NHEJ) is a prerequisite for the proper development of the central nervous system and the adaptive immune system. Yet, mice with Xlf or PAXX loss of function are viable and present with very mild immune phenotypes, although their lymphoid cells are sensitive to ionizing radiation attesting for the role of these factors in NHEJ. In contrast, we show here that mice defective for both Xlf and PAXX are embryonically lethal owing to a massive apoptosis of post-mitotic neurons, a situation reminiscent to XRCC4 or DNA Ligase IV KO conditions...
October 27, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29059378/characterization-of-the-aplf-fha-xrcc1-phosphopeptide-interaction-and-its-structural-and-functional-implications
#5
Kyungmin Kim, Lars C Pedersen, Thomas W Kirby, Eugene F DeRose, Robert E London
Aprataxin and PNKP-like factor (APLF) is a DNA repair factor containing a forkhead-associated (FHA) domain that supports binding to the phosphorylated FHA domain binding motifs (FBMs) in XRCC1 and XRCC4. We have characterized the interaction of the APLF FHA domain with phosphorylated XRCC1 peptides using crystallographic, NMR, and fluorescence polarization studies. The FHA-FBM interactions exhibit significant pH dependence in the physiological range as a consequence of the atypically high pK values of the phosphoserine and phosphothreonine residues and the preference for a dianionic charge state of FHA-bound pThr...
October 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29050484/enos-and-xrcc4-vntr-variants-contribute-to-formation-of-nicotine-dependence-and-or-schizophrenia
#6
S Pehlivan, M A Uysal, P C Aydin, M Pehlivan, A F Nursal, H Yavuzlar, S Kurnaz, U Sever, F K Yavuz, S Uysal, N Aydin
BACKGROUND: This study aimed to evaluate whether VNTR variants in the Endothelial Nitric Oxide Synthase (eNOS) and the XRCC4 gene play any role in nicotine dependence (ND) and/or Schizophrenia+ND (Sch+ND) ethiopathogenesis. METHODS: Present study included 100 individuals with ND, 60 patients with Sch+ND, and 70 healthy controls. These variants were analyzed using PCR. RESULTS: The cases with ND had higher eNOS VNTR-BB genotype than the healthy control subjects (p = 0...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29037125/signature-of-genetic-associations-in-oral-cancer
#7
Vishwas Sharma, Amrita Nandan, Amitesh Kumar Sharma, Harpreet Singh, Mausumi Bharadwaj, Dhirendra Narain Sinha, Ravi Mehrotra
Oral cancer etiology is complex and controlled by multi-factorial events including genetic events. Candidate gene studies, genome-wide association studies, and next-generation sequencing identified various chromosomal loci to be associated with oral cancer. There is no available review that could give us the comprehensive picture of genetic loci identified to be associated with oral cancer by candidate gene studies-based, genome-wide association studies-based, and next-generation sequencing-based approaches...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29035403/-polymorphism-of-genes-encoding-proteins-of-dna-repair-vs-occupational-and-environmental-exposure-to-lead-arsenic-and-pesticides
#8
REVIEW
Karol Bukowski, Katarzyna Woźniak
Genetic polymorphism is associated with the occurrence of at least 2 different alleles in the locus with a frequency higher than 1% in the population. Among polymorphisms we can find single nucleotide polymorphism (SNP) and polymorphism of variable number of tandem repeats. The presence of certain polymorphisms in genes encoding DNA repair enzymes is associated with the speed and efficiency of DNA repair and can protect or expose humans to the effects provoked by xenobiotics. Chemicals, such as lead, arsenic pesticides are considered to exhibit strong toxicity...
October 12, 2017: Medycyna Pracy
https://www.readbyqxmd.com/read/28993682/olaparib-modulates-dna-repair-efficiency-sensitizes-cervical-cancer-cells-to-cisplatin-and-exhibits-anti-metastatic-property
#9
Chandra Bhushan Prasad, Shyam Babu Prasad, Suresh Singh Yadav, Laxmi Kant Pandey, Sunita Singh, Satyajit Pradhan, Gopeshwar Narayan
PARP1 trapping at DNA lesion by pharmacological inhibitors has been exploited in several cancers exhibiting defects in DNA repair mechanisms. PARP1 hyperactivation is involved in therapeutic resistance in multiple cancers. The role of PARP1 in cervical cancer (CC) resistance and implication of PARP inhibitor is yet to be elucidated. Our data demonstrates significantly higher expression of PARP1 in primary cervical tumors and CC cell lines SiHa and ME180. Upon cisplatin treatment CC cells display significant overexpression of PARP1 and its hyperactivation...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28992182/association-of-dna-repair-gene-polymorphisms-with-genotoxic-stress-in-underground-coal-miners
#10
Maxim Yu Sinitsky, Varvara I Minina, Maxim A Asanov, Arseniy E Yuzhalin, Anastasia V Ponasenko, Vladimir G Druzhinin
In underground coal mining, numerous harmful substances and ionising radiation pose a major threat to the occupational safety and health of workers. Because cell DNA repair machinery eliminates genotoxic stress conferred by these agents, we examined whether single nucleotide polymorphisms in hOGG1 (rs1052133), XRCC1 (rs25487), ADPRT (rs1136410), XRCC4 (rs6869366) and LIG4 (rs1805388) genes modulate the genotoxic damage assessed by the cytokinesis-block micronucleus assay in lymphocytes from 143 underground coal miners and 127 healthy non-exposed males...
August 8, 2017: Mutagenesis
https://www.readbyqxmd.com/read/28963924/efficient-repair-of-dna-double-strand-breaks-in-individuals-from-high-level-natural-radiation-areas-of-kerala-coast-south-west-india
#11
Vinay Jain, Divyalakshmi Saini, P R Vivek Kumar, G Jaikrishan, Birajalaxmi Das
High level natural radiation areas (HLNRA) of Kerala coastal strip (55km long and 0.5km wide) in southwest India exhibit wide variations in the level of background dose (< 1.0-45.0mGy/year) due to thorium deposits in the beach sand. The areas with ≤1.5mGy/year are considered as normal level natural radiation area (NLNRA), whereas areas with >1.5mGy/year are HLNRA. Individuals belonging to HLNRA were stratified into two groups, Low dose group (LDG: 1.51-5.0mGy/year) and high dose group (HDG: >5.0mGy/year)...
September 20, 2017: Mutation Research
https://www.readbyqxmd.com/read/28930678/dna-ligase-iv-guides-end-processing-choice-during-nonhomologous-end-joining
#12
Michael P Conlin, Dylan A Reid, George W Small, Howard H Chang, Go Watanabe, Michael R Lieber, Dale A Ramsden, Eli Rothenberg
Nonhomologous end joining (NHEJ) must adapt to diverse end structures during repair of chromosome breaks. Here, we investigate the mechanistic basis for this flexibility. DNA ends are aligned in a paired-end complex (PEC) by Ku, XLF, XRCC4, and DNA ligase IV (LIG4); we show by single-molecule analysis how terminal mispairs lead to mobilization of ends within PECs and consequent sampling of more end-alignment configurations. This remodeling is essential for direct ligation of damaged and mispaired ends during cellular NHEJ, since remodeling and ligation of such ends both require a LIG4-specific structural motif, insert1...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28846869/xlf-cernunnos-an-important-but-puzzling-participant-in-the-nonhomologous-end-joining-dna-repair-pathway
#13
REVIEW
Vijay Menon, Lawrence F Povirk
DNA double strand breaks (DSBs) are one of the most deleterious DNA lesions that promote cell death, genomic instability and carcinogenesis. The two major cellular mechanisms that repair DSBs are Nonhomologous End-Joining (NHEJ) and Homologous Recombination Repair (HRR). NHEJ is the predominant pathway, in which XLF (also called Cernunnos) is a key player. Patients with XLF mutation exhibit microcephaly, lymphopenia, and growth retardation, and are immunodeficient and radiosensitive. During NHEJ, XLF interacts with XRCC4-Ligase IV, stimulates its ligase activity, and forms DNA-binding filaments of alternating XLF and XRCC4 dimers that may serve to align broken DNA and promote ligation of noncomplementary ends...
October 2017: DNA Repair
https://www.readbyqxmd.com/read/28796378/functional-genetic-variants-of-xrcc4-and-ercc1-predict-survival-of-gastric-cancer-patients-treated-with-chemotherapy-by-regulating-the-gene-expression
#14
Lei Cheng, Lixin Qiu, Mengyun Wang, Ruoxin Zhang, Menghong Sun, Xiaodong Zhu, Yanong Wang, Qingyi Wei
DNA repair protects genomic integrity and may modulate chemotherapy efficacy. Few large-scale studies have evaluated predictive roles of genetic variants of DNA repair genes in survival of Chinese gastric cancer (GCa) patients treated with chemotherapy. Here, we assessed the roles of 35 single nucleotide polymorphisms (SNPs) in DNA repair genes in survival of 1002 GCa patients, of whom 694 received chemotherapy and 308 did not. Among patients receiving chemotherapy, the ERCC1 rs2298881A allele was associated with a better survival [hazards ratio (HR) = 0...
August 10, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28780472/different-profiles-of-the-mrna-levels-of-dna-repair-genes-in-mcf-7-and-sh-sy5y-cells-after-treatment-with-combination-of-cisplatin-50-hz-electromagnetic-field-and-bleomycin
#15
Fatemeh Sanie-Jahromi, Mostafa Saadat
Neurotoxicity is known to be a major dose-limiting adverse effect of cisplatin (CDDP), alone or in combination with other chemicals. DNA repair capacity serve as a neuroprotective factor against CDDP. The purpose of this study was to evaluate the effect of 50-Hz electromagnetic field (EMF) in combination with CDDP and bleomycin (Bleo) on expression of some of DNA repair genes (GADD45A, XRCC1, XRCC4, Ku70, Ku80, DNA-PKcs and LIG4) in MCF-7 (breast cancer) and SH-SY5Y (neuroblastoma) cell lines. MCF-7 and SH-SY5Y cells were pre-treated with CDDP in the presence or absence of EMF and then exposed to different concentration of Bleo...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28759779/synthetic-lethality-between-murine-dna-repair-factors-xlf-and-dna-pkcs-is-rescued-by-inactivation-of-ku70
#16
Mengtan Xing, Magnar Bjørås, Jeremy A Daniel, Frederick W Alt, Valentyn Oksenych
DNA double-strand breaks (DSBs) are recognized and repaired by the Classical Non-Homologous End-Joining (C-NHEJ) and Homologous Recombination pathways. C-NHEJ includes the core Ku70 and Ku80 (or Ku86) heterodimer that binds DSBs and thus promotes recruitment of accessory downstream NHEJ factors XLF, PAXX, DNA-PKcs, Artemis and other core subunits, XRCC4 and DNA Ligase 4 (Lig4). In the absence of core C-NHEJ factors, DNA repair can be performed by Alternative End-Joining, which likely depends on DNA Ligase 1 and DNA Ligase 3...
September 2017: DNA Repair
https://www.readbyqxmd.com/read/28700650/sulforaphane-enhances-irradiation-effects-in-terms-of-perturbed-cell-cycle-progression-and-increased-dna-damage-in-pancreatic-cancer-cells
#17
Patrick Naumann, Jakob Liermann, Franco Fortunato, Thomas E Schmid, Klaus-Josef Weber, Jürgen Debus, Stephanie E Combs
BACKGROUND: Sulforaphane (SFN), an herbal isothiocyanate enriched in cruciferous vegetables like broccoli and cauliflower, has gained popularity for its antitumor effects in cell lines such as pancreatic cancer. Antiproliferative as well as radiosensitizing properties were reported for head and neck cancer but little is known about its effects in pancreatic cancer cells in combination with irradiation (RT). METHODS: In four established pancreatic cancer cell lines we investigated clonogenic survival, analyzed cell cycle distribution and compared DNA damage via flow cytometry and western blot after treatment with SFN and RT...
2017: PloS One
https://www.readbyqxmd.com/read/28696258/effects-of-dna-end-configuration-on-xrcc4-dna-ligase-iv-and-its-stimulation-of-artemis-activity
#18
Christina A Gerodimos, Howard H Y Chang, Go Watanabe, Michael R Lieber
In humans, nonhomologous DNA end-joining (NHEJ) is the major pathway by which DNA double-strand breaks are repaired. Recognition of each broken DNA end by the DNA repair protein Ku is the first step in NHEJ, followed by the iterative binding of nucleases, DNA polymerases, and the XRCC4-DNA ligase IV (X4-LIV) complex in an order influenced by the configuration of the two DNA ends at the break site. The endonuclease Artemis improves joining efficiency by functioning in a complex with DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) that carries out endonucleolytic cleavage of 5' and 3' overhangs...
August 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28645371/ensemble-and-single-molecule-analysis-of-non-homologous-end-joining-in-frog-egg-extracts
#19
Thomas G W Graham, Johannes C Walter, Joseph J Loparo
Non-homologous end joining (NHEJ) repairs the majority of DNA double-strand breaks in human cells, yet the detailed order of events in this process has remained obscure. Here, we describe how to employ Xenopus laevis egg extract for the study of NHEJ. The egg extract is easy to prepare in large quantities, and it performs efficient end joining that requires the core end joining proteins Ku, DNA-PKcs, XLF, XRCC4, and DNA ligase IV. These factors, along with the rest of the soluble proteome, are present at endogenous concentrations, allowing mechanistic analysis in a system that begins to approximate the complexity of cellular end joining...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28526069/xlf-mediated-nhej-activity-in-hepatocellular-carcinoma-therapy-resistance
#20
Sitian Yang, Xiao Qi Wang
BACKGROUND: DNA repair pathways are used by cancer cells to overcome many standard anticancer treatments, causing therapy resistance. Here, we investigated the role of XRCC4-like factor (XLF), a core member of the non-homologous end joining (NHEJ) repair pathway, in chemoresistance in hepatocellular carcinoma (HCC). METHODS: qRT-PCR analysis and western blotting were performed to detect expression levels of genes and proteins related to NHEJ. NHEJ repair capacity was assessed in vitro (cell-free) and in vivo by monitoring the activity of the NHEJ pathway...
May 19, 2017: BMC Cancer
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