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Juan A Montero, Cristina Sanchez-Fernandez, Carlos I Lorda-Diez, Juan A Garcia-Porrero, Juan M Hurle
DNA damage independent of caspase activation accompanies programmed cell death in different vertebrate embryonic organs. We analyzed the significance of DNA damage during the regression of the interdigital tissue, which sculpts the digits in the embryonic limb. Interdigit remodeling involves oxidative stress, massive apoptosis and cell senescence. Phosphorylation of H2AX mediated by ATM precedes caspase dependent apoptosis and cell senescence during interdigit regression. The association of γH2AX with other downstream DNA repair factors, including MDC1, Rad50 and 53BP1 suggests a defensive response of cells against DNA damage...
October 18, 2016: Scientific Reports
Anna Sobiepanek, Małgorzata Milner-Krawczyk, Konstancja Bobecka-Wesołowska, Tomasz Kobiela
The usage of active compounds of dietary phytochemicals in prevention of UV-induced skin diseases is increasingly gaining attention in the development of skin care products. The purpose of this study was to measure the influence of delphinidin (as a botanical agent) on the cell mechanical properties evaluated by the atomic force microscopy (AFM) technique in the immortalized human keratinocyte cell line (HaCaT) exposed to UVB radiation. The cells were treated with various doses of UVB radiation with and without pre and post-treatment with selected concentrations of delphinidin...
September 29, 2016: Journal of Photochemistry and Photobiology. B, Biology
Daniel Durocher, Laurence Pelletier
In this issue of Molecular Cell, Cuella-Martin et al. (2016) revisit the role of 53BP1 in p53-dependent responses and find that these functions are separable from its widely known function in DNA repair.
October 6, 2016: Molecular Cell
Christos Coucoravas, Soniya Dhanjal, Sofia Henriksson, Stefanie Böhm, Marianne Farnebo
The cellular response to DNA double-strand breaks is orchestrated by the protein kinase ATM, which phosphorylates key actors in the DNA repair network. WRAP53β is a multifunctional protein that controls trafficking of factors to Cajal bodies, telomeres and DNA double-strand breaks but what regulates the involvement of WRAP53β in these separate processes remains unclear. Here, we show that in response to various types of DNA damage, including IR and UV, WRAP53β is phosphorylated on serine residue 64 by ATM with a time-course that parallels its accumulation at DNA lesions...
October 7, 2016: RNA Biology
Deepu Oommen, Nicholas J F Dodd, Dennis Yiannakis, Rana Moyeed, Awadhesh N Jha
Auranofin, an organogold compound classified as an anti-rheumatic agent is under phase 2 clinical trials for re-purposing to treat recurrent epithelial ovarian cancer. We have reported earlier that Breast cancer 1, early onset (BRCA1) mutant ovarian cancer cells exhibit increased sensitivity to auranofin. BRCA1 is a DNA repair protein whose functional status is critical in the prognosis of ovarian cancer. Apart from DNA repair capability of cancer cells, membrane fluidity is also implicated in modulating resistance to chemotherapeutics...
October 2016: Mutation Research
Kathleen A Bridges, Xingxing Chen, Huifeng Liu, Crosby Rock, Thomas A Buchholz, Stuart D Shumway, Heath D Skinner, Raymond E Meyn
Radiotherapy is commonly used to treat a variety of solid tumors but improvements in the therapeutic ratio are sorely needed. The aim of this study was to assess the Chk1 kinase inhibitor, MK-8776, for its ability to radiosensitize human tumor cells. Cells derived from NSCLC and HNSCC cancers were tested for radiosensitization by MK-8776. The ability of MK-8776 to abrogate the radiation-induced G2 block was determined using flow cytometry. Effects on repair of radiation-induced DNA double strand breaks (DSBs) were determined on the basis of rad51, γ-H2AX and 53BP1 foci...
September 28, 2016: Oncotarget
Michal Malewicz
No abstract text is available yet for this article.
September 30, 2016: Cell Death and Differentiation
Minxing Li, Francesca Cole, Dharm S Patel, Sarah M Misenko, Joonyoung Her, Amy Malhowski, Ali Alhamza, Haiyan Zheng, Richard Baer, Thomas Ludwig, Maria Jasin, André Nussenzweig, Lourdes Serrano, Samuel F Bunting
BRCA1 mutations strongly predispose affected individuals to breast and ovarian cancer, but the mechanism by which BRCA1 acts as a tumor suppressor is not fully understood. Homozygous deletion of exon 2 of the mouse Brca1 gene normally causes embryonic lethality, but we show that exon 2-deleted alleles of Brca1 are expressed as a mutant isoform that lacks the N-terminal RING domain. This "RING-less" BRCA1 protein is stable and efficiently recruited to the sites of DNA damage. Surprisingly, robust RAD51 foci form in cells expressing RING-less BRCA1 in response to DNA damage, but the cells nonetheless display the substantial genomic instability...
September 26, 2016: EMBO Reports
Lukáš Jakl, Pavel Lobachevsky, Lenka Vokálová, Matúš Durdík, Eva Marková, Igor Belyaev
PURPOSE: Ionizing radiation-induced foci (IRIF) known also as DNA repair foci represent the most sensitive and specific assay for assessing DNA double-strand break (DSB). IRIF are usually visualized and enumerated with the aid of fluorescence microscopy using antibodies to phosphorylated γH2AX and 53BP1. Although several approaches and software packages were developed for quantification of IRIF, not one of them was commonly accepted and inter-laboratory variability in the outputs was reported...
September 20, 2016: International Journal of Radiation Biology
Ruoxi Hong, Fei Ma, Weimin Zhang, Xiying Yu, Qing Li, Yang Luo, Changjun Zhu, Wei Jiang, Binghe Xu
BACKGROUND: Mutations in DNA damage response factors BRCA1 and BRCA2 confer sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors in breast and ovarian cancers. BRCA1/BRCA2-defective tumors can exhibit resistance to PARP inhibitors via multiple mechanisms, one of which involves loss of 53BP1. Deficiency in the DNA damage response factor ataxia-telangiectasia mutated (ATM) can also sensitize tumors to PARP inhibitors, raising the question of whether the presence or absence of 53BP1 can predict sensitivity of ATM-deficient breast cancer to these inhibitors...
2016: BMC Cancer
Soňa Legartová, Petra Sehnalová, Barbora Malyšková, Thomas Küntziger, Philippe Collas, Dušan Cmarko, Ivan Raška, Dmitry V Sorokin, Stanislav Kozubek, Eva Bártová
Cover: The cover image, by Eva Bártová et al., is based on the Article Localized Movement and Levels of 53BP1 Protein Are Changed by γ-irradiation in PML Deficient Cells, DOI: 10.1002/jcb.25551.
November 2016: Journal of Cellular Biochemistry
Zacharenia Nikitaki, Vladimir Nikolov, Ifigeneia V Mavragani, Emil Mladenov, Anastasios Mangelis, Danae A Laskaratou, Georgios I Fragkoulis, Christine E Hellweg, Olga A Martin, Dimitris Emfietzoglou, Vasiliki I Hatzi, Georgia I Terzoudi, George Iliakis, Alexandros G Georgakilas
Detrimental effects of ionizing radiation (IR) are correlated to the varying efficiency of IR to induce complex DNA damage. A double strand break (DSB) can be considered the simpler form of complex DNA damage. These types of damage can consist of double strand breaks (DSBs), single strand breaks (SSBs) and/or non-DSB lesions such as base damages and apurinic/apyrimidinic (AP; abasic) sites in different combinations. Enthralling theoretical (Monte Carlo simulations) and experimental evidence suggests an increase of the complexity of DNA damage and therefore repair resistance with linear energy transfer (LET)...
September 5, 2016: Free Radical Research
Katharine H Wrighton
No abstract text is available yet for this article.
October 2016: Nature Reviews. Molecular Cell Biology
Johanna Selvaratnam, Bernard Robaire
Advanced paternal age is associated with increased complications in pregnancy and genetic diseases in offspring. Oxidative stress is a major contributor to the damage accumulated in sperm during aging. Complex networks of antioxidants regulate reactive oxygen species (ROS) in the testis. While mounting evident shows that redox dysfunction compromises the quality of developing male germ cells, the mechanisms by which aging causes this remain unclear. Furthermore, therapies to successfully alleviate aging-associated loss in germ cell quality are limited...
November 2016: Experimental Gerontology
Eleonora Croco, Silvia Marchionni, Martine Bocchini, Cristina Angeloni, Thomas Stamato, Claudio Stefanelli, Silvana Hrelia, Christian Sell, Antonello Lorenzini
In order to examine potential differences in genomic stability, we have challenged fibroblasts derived from five different mammalian species of variable longevity with the genotoxic agents, etoposide and neocarzinostatin. We report that cells from longer-lived species exhibit more tumor protein p53 binding protein 1 (53BP1) foci for a given degree of DNA damage relative to shorter-lived species. The presence of a greater number of 53BP1 foci was associated with decreased DNA fragmentation and a lower percentage of cells exhibiting micronuclei...
August 29, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Shubhankar Suman, Santosh Kumar, Prosper N'Gouemo, Kamal Datta
Binge drinking is known to cause damage in critical areas of the brain, including the hippocampus, which is important for relational memory and is reported to be sensitive to alcohol toxicity. However, the roles of DNA double-strand break (DSB) and its repair pathways, homologous recombination (HR), and non-homologous end joining (NHEJ) in alcohol-induced hippocampal injury remain to be elucidated. The purpose of this first study was to assess alcohol-induced DNA DSB and the mechanism by which alcohol affects DSB repair pathways in rat hippocampus...
August 2016: Alcohol
(no author information available yet)
The 53BP1-USP28 complex enhances p53-dependent transcription to promote tumor suppression.
October 2016: Cancer Discovery
Aurélie Henry, Marie-Julie Nokin, Natacha Leroi, François Lallemand, Jérémy Lambert, Nicolas Goffart, Patrick Roncarati, Elettra Bianchi, Paul Peixoto, Arnaud Blomme, Andrei Turtoi, Olivier Peulen, Yvette Habraken, Félix Scholtes, Philippe Martinive, Philippe Delvenne, Bernard Rogister, Vincent Castronovo, Akeila Bellahcène
Glioblastoma (GBM) represents the most aggressive and common solid human brain tumor. We have recently demonstrated the importance of osteopontin (OPN) in the acquisition/maintenance of stemness characters and tumorigenicity of glioma initiating cells. Consultation of publicly available TCGA database indicated that high OPN expression correlated with poor survival in GBM patients. In this study, we explored the role of OPN in GBM radioresistance using an OPN-depletion strategy in U87-MG, U87-MG vIII and U251-MG human GBM cell lines...
August 22, 2016: Oncotarget
Wael Jdey, Sylvain Thierry, Christophe Russo, Flavien Devun, Muthana Al Abo, Patricia Noguiez-Hellin, Jian-Sheng Sun, Emmanuel Barillot, Andrei Zinovyev, Inna Kuperstein, Yves Pommier, Marie Dutreix
PURPOSE: Cancer treatments using tumor defects in DNA repair pathways have shown promising results but are restricted to small subpopulations of patients. The most advanced drugs in this field are Poly(ADP-Ribose) Polymerase (PARP) inhibitors (PARPi), which trigger synthetic lethality in tumors with Homologous Recombination (HR) deficiency. Using AsiDNA, an inhibitor of HR and Non Homologous End Joining, together with PARPi should allow bypassing the genetic restriction for PARPi efficacy...
August 24, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Kensuke Otsuka, Keiji Suzuki
The protection of intestinal epithelial cells from the lethal effects induced by high-dose radiation is an important issue in radiotherapy and in the treatment of acute radiation syndrome. However, the effects of middle- and low-dose radiation on intestinal epithelial cells remain unclear. Because the accumulation of DNA damage in intestinal stem cells may be crucial for the development of cancer-initiating cells, it is important to understand the kinetics of DNA repair and tissue response (which are involved in the elimination of damaged cells and tissue injury repair) to middle- to low-dose irradiation...
September 2016: Radiation Research
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