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https://www.readbyqxmd.com/read/28231404/express-or-repress-the-transcriptional-dilemma-of-damaged-chromatin
#1
Ilaria Capozzo, Fabio Iannelli, Sofia Francia, Fabrizio d'Adda di Fagagna
The fine modulation of transcriptional activity around DNA lesions is essential to carefully regulate the crosstalk between transcription, the DNA damage response, and DNA repair, particularly when the lesion occurs next to, or within, actively transcribed genes. Recently, several studies have been carried out to investigate how DNA lesions have an impact on local transcription, but the emerging model remains incomplete. Transcription of genes around damaged DNA is actively down-regulated by the DNA damage response through different mechanisms, which appear specific to the chromatin context, the type of DNA damage or its complexity...
February 23, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28231273/periovulatory-follicular-fluid-levels-of-estradiol-trigger-inflammatory-and-dna-damage-responses-in-oviduct-epithelial-cells
#2
Sergio E Palma-Vera, Jennifer Schoen, Shuai Chen
OBJECTIVE: Ovarian steroid hormones (mainly E2 and P4) regulate oviduct physiology. Serum-E2 acts on the oviduct epithelium from the basolateral cell compartment. Upon ovulation, the apical compartment of the oviduct epithelium is temporarily exposed to follicular fluid, which contains much higher levels of E2 than serum. The aim of this study was to evaluate the effects of human periovulatory follicular fluid levels of E2 on oviduct epithelial cells using two porcine in vitro models...
2017: PloS One
https://www.readbyqxmd.com/read/28213501/immature-lymphocytes-inhibit-rag1-and-rag2-transcription-and-v-d-j-recombination-in-response-to-dna-double-strand-breaks
#3
Megan R Fisher, Adrian Rivera-Reyes, Noah B Bloch, David G Schatz, Craig H Bassing
Mammalian cells have evolved a common DNA damage response (DDR) that sustains cellular function, maintains genomic integrity, and suppresses malignant transformation. In pre-B cells, DNA double-strand breaks (DSBs) induced at Igκ loci by the Rag1/Rag2 (RAG) endonuclease engage this DDR to modulate transcription of genes that regulate lymphocyte-specific processes. We previously reported that RAG DSBs induced at one Igκ allele signal through the ataxia telangiectasia mutated (ATM) kinase to feedback-inhibit RAG expression and RAG cleavage of the other Igκ allele...
February 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28203282/the-role-of-dexlansoprazole-modified-release-in-the-management-of-gastroesophageal-reflux-disease
#4
REVIEW
Ronnie Fass, Rosita Frazier
Dexlansoprazole modified-release (MR) is the R-enantiomer of lansoprazole and is currently the only proton-pump inhibitor (PPI) with a novel dual delayed release (DDR) formulation. Overall, dexlansoprazole MR demonstrates a similar safety and side-effect profile as lansoprazole. Dexlansoprazole MR has been shown to be highly efficacious in healing erosive esophagitis, maintaining healed esophageal mucosa in patients with erosive esophagitis and controlling symptoms of patients with nonerosive reflux disease (NERD)...
February 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28202068/the-dna-damage-response-promotes-polyomavirus-jc-infection-by-nucleus-to-cytoplasm-nf-kappab-activation
#5
Martyn K White, Anna Bellizzi, Gabriele Ibba, Valeria Pietropaolo, Anna T Palamara, Hassen S Wollebo
BACKGROUND: Infection of glial cells by human neurotropic polyomavirus JC (JCV), the causative agent of the CNS demyelinating disease progressive multifocal leukoencephalopathy (PML), rapidly inflicts damage to cellular DNA. This activates DNA damage response (DDR) signaling including induction of expression of DNA repair factor Rad51. We previously reported that Rad51 co-operates with the transcription factor NF-κB p65 to activate JCV early transcription. Thus Rad51 induction by JCV infection may provide positive feedback for viral activation early in JCV infection...
February 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28193847/dna-damage-response-independent-role-for-mdc1-in-maintaining-genomic-stability
#6
Zhiguo Li, Chen Shao, Yifan Kong, Colin Carlock, Nihal Ahmad, Xiaoqi Liu
MDC1 is a central player in checkpoint activation and subsequent DNA repair following DNA damage. Although MDC1 has been extensively studied, much of its known functions to date pertains to the DNA damage response (DDR) pathway. Herein, we report a novel function of phosphorylated MDC1, independent of ATM and DNA damage, which is required for proper mitotic progression and maintenance of genomic stability. We demonstrate that MDC1 is an in vivo target of Plk1 and that the phosphorylated MDC1 is dynamically localized to nuclear envelopes, centrosomes, kinetochores and the midbodies...
February 13, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28186195/cenp-a-chromatin-disassembly-in-stressed-and-senescent-murine-cells
#7
Sabrine Hédouin, Giacomo Grillo, Ivana Ivkovic, Guillaume Velasco, Claire Francastel
Centromeres are chromosomal domains essential for genomic stability. We report here the remarkable transcriptional and epigenetic perturbations at murine centromeres in genotoxic stress conditions. A strong and selective transcriptional activation of centromeric repeats is detected within hours. This is followed by disorganization of centromeres with striking delocalization of nucleosomal CENP-A, the key determinant of centromere identity and function, in a mechanism requiring active transcription of centromeric repeats, the DNA Damage Response (DDR) effector ATM and chromatin remodelers/histone chaperones...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28180124/does-a-negative-emergency-celiotomy-exclude-the-possibility-of-significant-diaphragmatic-injury-a-case-report-and-review-of-the-literature
#8
Alireza Hamidian Jahromi, David Pennywell, John T Owings
INTRODUCTION: Diaphragmatic rupture (DR) is an uncommon, potentially serious complication following blunt or penetrating abdominal trauma. Even with a high index of suspicion, the diagnosis of DR can easily be missed for a long period post injury. Delayed or missed diagnosis [delayed diagnosis of diaphragmatic rupture (DDDR)] and delayed diaphragmatic rupture (DDR) are possible explanations in cases where the initial operative exploration fails to show the diaphragmatic damage. CASE PRESENTATION: Here we present a patient with suspected DR that was not seen on initial open abdominal exploration, but was suggested by subsequent serial imaging...
September 2016: Trauma Monthly
https://www.readbyqxmd.com/read/28166834/downregulation-of-mir-130b-301b-cluster-is-mediated-by-aberrant-promoter-methylation-and-impairs-cellular-senescence-in-prostate-cancer
#9
João Ramalho-Carvalho, Inês Graça, Antonio Gomez, Jorge Oliveira, Rui Henrique, Manel Esteller, Carmen Jerónimo
BACKGROUND: Numerous DNA-damaging cellular stresses, including oncogene activation and DNA-damage response (DDR), may lead to cellular senescence. Previous observations linked microRNA deregulation with altered senescent patterns, prompting us to investigate whether epigenetic repression of microRNAs expression might disrupt senescence in prostate cancer (PCa) cells. METHODS: Differential methylation mapping in prostate tissues was carried using Infinium HumanMethylation450 BeadChip...
February 6, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28166748/body-mass-index-modifies-the-relationship-between-%C3%AE-h2ax-a-dna-damage-biomarker-and-pathological-complete-response-in-triple-negative-breast-cancer
#10
Maddalena Barba, Patrizia Vici, Laura Pizzuti, Luigi Di Lauro, Domenico Sergi, Anna Di Benedetto, Cristiana Ercolani, Francesca Sperati, Irene Terrenato, Claudio Botti, Lucia Mentuccia, Laura Iezzi, Teresa Gamucci, Clara Natoli, Ilio Vitale, Marcella Mottolese, Ruggero De Maria, Marcello Maugeri-Saccà
BACKGROUND: Body mass index (BMI) is largely investigated as a prognostic and predictive factor in triple-negative breast cancer (TNBC). Overweight and obesity are linked to a variety of pathways regulating tumor-promoting functions, including the DNA damage response (DDR). The DDR physiologically safeguards genome integrity but, in a neoplastic background, it is aberrantly engaged and protects cancer cells from chemotherapy. We herein verified the role of BMI on a previously assessed association between DDR biomarkers and pathological complete response (pCR) in TNBC patients treated with neoadjuvant chemotherapy (NACT)...
February 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28157626/evaluation-of-18-f-atri-as-pet-tracer-for-in-vivo-imaging-of-atr-in-mouse-models-of-brain-cancer
#11
Giuseppe Carlucci, Brandon Carney, Ahmad Sadique, Axel Vansteene, Jun Tang, Thomas Reiner
RATIONALE: Ataxia telangiectasia and Rad3-related (ATR) threonine serine kinase is one of the key elements in orchestrating the DNA damage response (DDR). As such, inhibition of ATR can amplify the effects of chemo- and radiation-therapy, and several ATR inhibitors (ATRi) have already undergone clinical testing in cancer. For more accurate patient selection, monitoring and staging, real-time in vivo imaging of ATR could be invaluable; the development of appropriate imaging agents has remained a major challenge...
January 16, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28155336/a-microemulsion-co-loaded-with-schizandrin-a-docetaxel-enhances-esophageal-carcinoma-treatment-through-overcoming-multidrug-resistance
#12
Xiangyu Su, Chanchan Gao, Fangfang Shi, Xiaoyao Feng, Lin Liu, Ding Qu, Cailian Wang
Multidrug resistance (MDR) is the major underlying cause of the low 5-year survival rate of esophageal carcinoma. In this study, we developed a novel microemulsion system (SD-ME) co-loaded with docetaxel (DTX) and Schizandrin A, a potent chemotherapeutic agent and a potential drug resistance modulator, respectively. In the physicochemical characterization studies, SD-ME displayed a well-defined spherical shape and size (56.62 ± 4.16 nm), a narrow polydispersity index (PDI, 0.132 ± 0.002), and a negative surface charge (-19...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28154131/a-pathway-of-targeted-autophagy-is-induced-by-dna-damage-in-budding-yeast
#13
Vinay V Eapen, David P Waterman, Amélie Bernard, Nathan Schiffmann, Enrich Sayas, Roarke Kamber, Brenda Lemos, Gonen Memisoglu, Jessie Ang, Allison Mazella, Silvia G Chuartzman, Robbie J Loewith, Maya Schuldiner, Vladimir Denic, Daniel J Klionsky, James E Haber
Autophagy plays a central role in the DNA damage response (DDR) by controlling the levels of various DNA repair and checkpoint proteins; however, how the DDR communicates with the autophagy pathway remains unknown. Using budding yeast, we demonstrate that global genotoxic damage or even a single unrepaired double-strand break (DSB) initiates a previously undescribed and selective pathway of autophagy that we term genotoxin-induced targeted autophagy (GTA). GTA requires the action primarily of Mec1/ATR and Rad53/CHEK2 checkpoint kinases, in part via transcriptional up-regulation of central autophagy proteins...
February 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28153919/function-of-the-plant-dna-polymerase-epsilon-in-replicative-stress-sensing-a-genetic-analysis
#14
Jose-Antonio Pedroza-Garcia, Christelle Mazubert, Ivan Del Olmo, Mickael Bourge, Séverine Domenichini, Rémi Bounon, Zakia Tariq, Etienne Delannoy, Manuel Piñeiro, Jose A Jarillo, Catherine Bergounioux, Moussa Benhamed, Cécile Raynaud
Faithful transmission of the genetic information is essential in all living organisms. DNA replication is therefore a critical step of cell proliferation, because of the potential occurrence of replication errors or DNA damage when progression of a replication fork is hampered causing replicative stress. Like other types of DNA damage, replicative stress activates the DNA Damage Response (DDR) a signaling cascade allowing cell cycle arrest and repair of lesions. The replicative DNA polymerase ε (Pol ε) was shown to activate the S-phase checkpoint in yeast in response to replicative stress, but whether this mechanism functions in multicellular eukaryotes remains unclear...
February 2, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28143445/hsp90-inhibition-sensitizes-head-and-neck-cancer-to-platin-based-chemoradiotherapy-by-modulation-of-the-dna-damage-response-resulting-in-chromosomal-fragmentation
#15
Martin McLaughlin, Holly E Barker, Aadil A Khan, Malin Pedersen, Magnus Dillon, David C Mansfield, Radhika Patel, Joan N Kyula, Shreerang A Bhide, Kate L Newbold, Christopher M Nutting, Kevin J Harrington
BACKGROUND: Concurrent cisplatin radiotherapy (CCRT) is a current standard-of-care for locally advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT is frequently ineffective in patients with advanced disease. It has previously been shown that HSP90 inhibitors act as radiosensitizers, but these studies have not focused on CCRT in HNSCC. Here, we evaluated the HSP90 inhibitor, AUY922, combined with CCRT. METHODS: The ability of AUY922 to sensitize to CCRT was assessed in p53 mutant head and neck cell lines by clonogenic assay...
January 31, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28140789/p53-and-rad9-the-dna-damage-response-and-regulation-of-transcription-networks
#16
Howard B Lieberman, Sunil K Panigrahi, Kevin M Hopkins, Li Wang, Constantinos G Broustas
The way cells respond to DNA damage is important since inefficient repair or misrepair of lesions can have deleterious consequences, including mutation, genomic instability, neurodegenerative disorders, premature aging, cancer or death. Whether damage occurs spontaneously as a byproduct of normal metabolic processes, or after exposure to exogenous agents, cells muster a coordinated, complex DNA damage response (DDR) to mitigate potential harmful effects. A variety of activities are involved to promote cell survival, and include DNA repair, DNA damage tolerance, as well as transient cell cycle arrest to provide time for repair before entry into critical cell cycle phases, an event that could be lethal if traversal occurs while damage is present...
January 31, 2017: Radiation Research
https://www.readbyqxmd.com/read/28137924/dna-damage-response-and-repair-gene-alterations-are-associated-with-improved-survival-in-patients-with-platinum-treated-advanced-urothelial-carcinoma
#17
Min Yuen Teo, Richard Bambury, Emily C Zabor, Emmet J Jordan, Hikmat A Al-Ahmadie, Mariel Boyd, Nancy Bouvier, Stephanie Mullane, Eugene K Cha, Nitin Roper, Irina Ostrovnaya, David M Hyman, Bernard H Bochner, Maria E Arcila, David B Solit, Michael F Berger, Dean F Bajorin, Joaquim Bellmunt, Gopa Iyer, Jonathan E Rosenberg
PURPOSE: Platinum-based chemotherapy remains the standard treatment for advanced urothelial carcinoma by inducing DNA damage. We hypothesize that somatic alterations in DNA damage response and repair (DDR) genes are associated with improved sensitivity to platinum-based chemotherapy. EXPERIMENTAL DESIGN: Patients with diagnosis of locally advanced and metastatic urothelial carcinoma treated with platinum-based chemotherapy who had exon sequencing with MSK-IMPACT assay were identified...
January 30, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28132856/nadph-oxidase-1-plays-a-key-role-in-keratinocyte-responses-to-ultraviolet-radiation-and-uvb-induced-skin-carcinogenesis
#18
Houssam Raad, Martin Serrano-Sanchez, Ghida Harfouche, Walid Mahfouf, Doriane Bortolotto, Vanessa Bergeron, Zeinab Kasraian, Lea Dousset, Mohsen Hosseini, Alain Taieb, Hamid Reza Rezvani
The NADPH oxidase (NOX) family enzymes are involved in several physiological functions. However, their roles in keratinocyte responses to ultraviolet (UV) radiation have not been clearly elucidated. This study demonstrates that, among other NOX family members, UVB irradiation results in a biphasic activation of NOX1 that plays a critical role in defining keratinocyte fate through the modulation of the DNA damage response (DDR) network. Indeed, suppression of both bursts of UVB-induced NOX1 activation by using a specific peptide inhibitor of NOX1 (InhNOX1) is associated with increased nucleotide excision repair (NER) efficiency and reduction of apoptosis, which is finally translated into decreased photocarcinogenesis...
January 26, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28130344/putting-phds-to-work-phf11-clears-the-way-for-exo1-in-double-strand-break-repair
#19
REVIEW
Karl E Zahn, Roger A Greenberg
In this issue of Genes & Development, Gong and colleagues (pp. 46-58) bring to light a functional role for plant homeodomain finger 11 (PHF11) in 5' end resection at DNA double-strand breaks (DSBs). Using the proteomics of isolated chromatin segments (PICh) technique to purify deprotected telomeres, PHF11 was enriched as cells mounted a DNA damage response (DDR) against exposed chromosome ends. The study reveals interactions between PHF11 and multiple DNA repair proteins and suggests that PHF11 mediates 5' end resection by negotiating RPA-coated DNA repair intermediates...
January 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28124509/a-novel-single-cell-method-provides-direct-evidence-of-persistent-dna-damage-in-senescent-cells-and-aged-mammalian-tissues
#20
Alessandro Galbiati, Christian Beauséjour, Fabrizio d'Adda di Fagagna
The DNA damage response (DDR) arrests cell cycle progression until DNA lesions, like DNA double-strand breaks (DSBs), are repaired. The presence of DSBs in cells is usually detected by indirect techniques that rely on the accumulation of proteins at DSBs, as part of the DDR. Such detection may be biased, as some factors and their modifications may not reflect physical DNA damage. The dependency on DDR markers of DSB detection tools has left questions unanswered. In particular, it is known that senescent cells display persistent DDR foci, that we and others have proposed to be persistent DSBs, resistant to endogenous DNA repair activities...
January 26, 2017: Aging Cell
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