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DNA damage response

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https://www.readbyqxmd.com/read/28340478/different-dna-damage-response-of-cis-and-trans-isomers-of-commonly-used-uv-filter-after-the-exposure-on-adult-human-liver-stem-cells-and-human-lymphoblastoid-cells
#1
Anežka Sharma, Katarína Bányiová, Pavel Babica, Naouale El Yamani, Andrew Richard Collins, Pavel Čupr
2-ethylhexyl 4-methoxycinnamate (EHMC), used in many categories of personal care products (PCPs), is one of the most discussed ultraviolet filters because of its endocrine-disrupting effects. EHMC is unstable in sunlight and can be transformed from trans-EHMC to emergent cis-EHMC. Toxicological studies are focusing only on trans-EHMC; thus the toxicological data for cis-EHMC are missing. In this study, the in vitro genotoxic effects of trans- and cis-EHMC on adult human liver stem cells HL1-hT1 and human-derived lymphoblastoid cells TK-6 using a high-throughput comet assay were studied...
March 21, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28340409/mitochondrial-dna-damage-and-oxidative-damage-in-hl-60-cells-exposed-to-900mhz-radiofrequency-fields
#2
Yulong Sun, Lin Zong, Zhen Gao, Shunxing Zhu, Jian Tong, Yi Cao
HL-60 cells, derived from human promyelocytic leukemia, were exposed to continuous wave 900MHz radiofrequency fields (RF) at 120μW/cm(2) power intensity for 4h/day for 5 consecutive days to examine whether such exposure is capable damaging the mitochondrial DNA (mtDNA) mediated through the production of reactive oxygen species (ROS). In addition, the effect of RF exposure was examined on 8-hydroxy-2'-dexoyguanosine (8-OHdG) which is a biomarker for oxidative damage and on the mitochondrial synthesis of adenosine triphosphate (ATP) which is the energy required for cellular functions...
March 7, 2017: Mutation Research
https://www.readbyqxmd.com/read/28340269/prevention-of-dna-damage-and-anticarcinogenic-activity-of-activia-%C3%A2-in-a-preclinical-model
#3
S M A Limeiras, F M Ogo, L A L Genez, C M Carreira, E J T Oliveira, L R Pessatto, S C Neves, J R Pesarini, L C Schweich, R A Silva, W B Cantero, A C M B Antoniolli-Silva, R J Oliveira
Colorectal cancer is a global public health issue. Studies have pointed to the protective effect of probiotics on colorectal carcinogenesis. Activia(®) is a lacto probiotic product that is widely consumed all over the world and its beneficial properties are related, mainly, to the lineage of traditional yoghurt bacteria combined with a specific bacillus, DanRegularis, which gives the product a proven capacity to intestinal regulation in humans. The aim of this study was to evaluate the antigenotoxic, antimutagenic, and anticarcinogenic proprieties of the Activia product, in response to damage caused by 1,2-dimethylhydrazine (DMH) in Swiss mice...
March 22, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28339978/ozone-sensitive-arabidopsis-mutants-with-deficiencies-in-photorespiratory-enzymes
#4
Shoko Saji, Srinivas Bathula, Akihiro Kubo, Masanori Tamaoki, Mitsuko Aono, Tomoharu Sano, Kazuo Tobe, Stefan Timm, Hermann Bauwe, Nobuyoshi Nakajima, Hikaru Saji
An ozone-sensitive mutant was isolated from T-DNA-tagged lines of Arabidopsis thaliana. The T-DNA was inserted at a locus on chromosome 3, where two genes encoding glycolate oxidases, GOX1 and GOX2, peroxisomal enzymes involved in photorespiration, reside contiguously. The amounts of the mutant's foliar transcripts for these genes were reduced, and glycolate oxidase activity was approximately 60% of that of the wild-type plants. No difference in growth and appearance was observed between the mutant and the wild-type plants under normal conditions with ambient air under a light intensity of 100 µmol photons m-2 s-1...
February 21, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28339401/is-huntingtin-dispensable-in-the-adult-brain
#5
Jeh-Ping Liu, Scott O Zeitlin
Huntingtin (HTT) is an essential protein during early embryogenesis and the development of the central nervous system (CNS). Conditional knock-out of mouse Huntingtin (Htt) expression in the CNS beginning during neural development, as well as reducing Htt expression only during embryonic and early postnatal stages, results in neurodegeneration in the adult brain. These findings suggest that HTT is important for the development and/or maintenance of the CNS, but they do not address the question of whether HTT is required specifically in the adult CNS for its normal functions and/or homeostasis...
March 21, 2017: Journal of Huntington's Disease
https://www.readbyqxmd.com/read/28339062/p53-microrna-374b-akt1-regulates-colorectal-cancer-cell-apoptosis-in-response-to-dna-damage
#6
Hangjun Gong, Yu Cao, Gang Han, Yun Zhang, Qing You, Yidong Wang, Yamin Pan
Colorectal cancer (CRC) has a rising morbidity worldwide and its resistance to chemotherapy has been observed in clinical treatment. Tumor suppressor p53 is well-studied in CRC, but little is known about its effects during DNA damage of CRC cells. This study was aimed at uncovering potential mechanisms of p53 regarding microRNA-374b and v-akt murine thymoma viral oncogene homolog 1 (AKT1) during DNA damage of CRC cells. CRC cells HCT116 and HT29 were transfected with p53-specific small interfering RNA (siRNA), p53 overexpression vector or miR-374b inhibitor, and then treated with 10 µM bleomycin (BLM) for 24 h to induce DNA damage...
March 21, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28338045/abnormal-levels-of-histone-methylation-in-the-retinas-of-diabetic-rats-are-reversed-by-minocycline-treatment
#7
Wenjun Wang, Simone Sidoli, Wenquan Zhang, Qing Wang, Leilei Wang, Ole N Jensen, Lin Guo, Xiaolu Zhao, Ling Zheng
In this study we quantified the alterations of retinal histone post-translational modifications (PTMs) in diabetic rats using a liquid chromatography - tandem mass spectrometry (LC-MS/MS) approach. Some diabetic rats were subsequently treated with minocycline, a tetracycline antibiotic, which has been shown to inhibit the diabetes-induced chronic inflammation in the retinas of rodents. We quantified 266 differentially modified histone peptides, including 48 out of 83 methylation marks with significantly different abundancein retinas of diabetic rats as compared to non-diabetic controls...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337983/self-inflicted-dna-double-strand-breaks-sustain-tumorigenicity-and-stemness-of-cancer-cells
#8
Xinjian Liu, Fang Li, Qian Huang, Zhengxiang Zhang, Ling Zhou, Yu Deng, Min Zhou, Donald E Fleenor, He Wang, Michael B Kastan, Chuan-Yuan Li
DNA double-strand breaks (DSBs) are traditionally associated with cancer through their abilities to cause chromosomal instabilities or gene mutations. Here we report a new class of self-inflicted DNA DSBs that can drive tumor growth irrespective of their effects on genomic stability. We discover a mechanism through which cancer cells cause DSBs in their own genome spontaneously independent of reactive oxygen species or replication stress. In this mechanism, low-level cytochrome c leakage from the mitochondria leads to sublethal activation of apoptotic caspases and nucleases, which causes DNA DSBs...
March 24, 2017: Cell Research
https://www.readbyqxmd.com/read/28337955/examining-the-in-vitro-efficacy-of-the-iap-antagonist-birinapant-as-a-single-agent-or-in-combination-with-dacarbazine-to-induce-melanoma-cell-death
#9
Vesna Vetma, Jan Rožanc, Emilie M Charles, Christian T Hellwig, Leonidas G Alexopoulos, Markus Rehm
Antagonists of inhibitor of apoptosis proteins (IAPs), alone or in combination with genotoxic therapeutics, have been shown to efficiently induce cell death in various solid tumours. The IAP antagonist birinapant is currently being tested in phase II clinical trials. We herein aimed to investigate the in vitro anti-tumour efficacy of dacarbazine, both as a single agent and in combination with birinapant, in melanoma cell lines. Covering clinically relevant drug concentration ranges, we conducted a total of 5400 measurements in a panel of 12 human melanoma cell lines representing different stages of disease progression...
March 23, 2017: Oncology Research
https://www.readbyqxmd.com/read/28337296/tumor-suppressor-p53-induces-mir-15a-processing-to-inhibit-neuronal-apoptosis-inhibitory-protein-naip-in-the-apoptotic-response-dna-damage-in-breast-cancer-cell
#10
Li Yang, Wei Zhao, Ping Wei, Wenshu Zuo, Shouhui Zhu
This study was aimed to investigate the functional role of miR-15a in breast cancer cells in response to DNA damage and to illustrate the possible potential underlying molecular mechanism(s). Human breast cancer cell lines MCF-7 cells and/or MDA-MB-231 cells were pre-treated with or without bleomycin. Cells were transfected with corresponding vectors. qRT-PCR was used to detect the expression of mRNA or miRNA, and immunoprecipitation and immunoblot analysis were performed to explore the status of protein association...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337249/cellular-homeostasis-and-antioxidant-response-in-epithelial-ht29-cells-on-titania-nanotube-arrays-surface
#11
Rabiatul Basria Smn Mydin, Srimala Sreekantan, Roshasnorlyza Hazan, Mustafa Fadzil Farid Wajidi, Ishak Mat
Cell growth and proliferative activities on titania nanotube arrays (TNA) have raised alerts on genotoxicity risk. Present toxicogenomic approach focused on epithelial HT29 cells with TNA surface. Fledgling cell-TNA interaction has triggered G0/G1 cell cycle arrests and initiates DNA damage surveillance checkpoint, which possibly indicated the cellular stress stimuli. A profound gene regulation was observed to be involved in cellular growth and survival signals such as p53 and AKT expressions. Interestingly, the activation of redox regulator pathways (antioxidant defense) was observed through the cascade interactions of GADD45, MYC, CHECK1, and ATR genes...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28336836/visible-light-responsive-platinum-containing-titania-nanoparticle-mediated-photocatalysis-induces-nucleotide-insertion-deletion-and-substitution-mutations
#12
Der-Shan Sun, Yao-Hsuan Tseng, Wen-Shiang Wu, Ming-Show Wong, Hsin-Hou Chang
Conventional photocatalysts are primarily stimulated using ultraviolet (UV) light to elicit reactive oxygen species and have wide applications in environmental and energy fields, including self-cleaning surfaces and sterilization. Because UV illumination is hazardous to humans, visible light-responsive photocatalysts (VLRPs) were discovered and are now applied to increase photocatalysis. However, fundamental questions regarding the ability of VLRPs to trigger DNA mutations and the mutation types it elicits remain elusive...
December 28, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28336775/nelf-e-is-recruited-to-dna-double-strand-break-sites-to-promote-transcriptional-repression-and-repair
#13
Samah W Awwad, Enas R Abu-Zhayia, Noga Guttmann-Raviv, Nabieh Ayoub
Double-strand breaks (DSBs) trigger rapid and transient transcription pause to prevent collisions between repair and transcription machineries at damage sites. Little is known about the mechanisms that ensure transcriptional block after DNA damage. Here, we reveal a novel role of the negative elongation factor NELF in blocking transcription activity nearby DSBs. We show that NELF-E and NELF-A are rapidly recruited to DSB sites. Furthermore, NELF-E recruitment and its repressive activity are both required for switching off transcription at DSBs...
March 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28336372/doxorubicin-targets-multiple-players-a-new-view-of-an-old-problem
#14
REVIEW
Donato Cappetta, Francesca Rossi, Elena Piegari, Federico Quaini, Liberato Berrino, Konrad Urbanek, Antonella De Angelis
Anthracycline cardiotoxicity remains a serious problem in paediatric and adult cancer survivors, and the advancement of cardio-oncology is a necessary step for an effective care of the patients that experience adverse cardiovascular effects. In this review, we discuss the multiple instruments used by clinicians that constitute the current strategies for primary and secondary prevention aiming at contrasting the onset of early and late doxorubicin-induced cardiotoxic events. The importance of early detection of cardiotoxicity and the following pharmacological therapy has been acknowledged with the emphasis put on impaired diastolic function, an increasingly recognized precocious sign of doxorubicin cardiotoxicity with an emerging scientific and clinical interest...
March 20, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28336131/modulating-the-dna-damage-response-to-improve-treatment-response-in-cervical-cancer
#15
L H Cossar, A G Schache, J M Risk, J J Sacco, N J Jones, R Lord
Cervical cancer is the fourth most common cause of cancer-related death in women worldwide and new therapeutic approaches are needed to improve clinical outcomes for this group of patients. Current treatment protocols for locally advanced and metastatic disease consist of ionising radiation and chemotherapy. Chemoradiation induces cytotoxic levels of DNA double-strand breaks, which activates programmed cell death via the DNA damage response (DDR). Cervical cancers are unique given an almost exclusive association with human papillomavirus (HPV) infection; a potent manipulator of the DDR, with the potential to alter tumour sensitivity to DNA-damaging agents and influence treatment response...
March 20, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28334900/cdk12-regulates-alternative-last-exon-mrna-splicing-and-promotes-breast-cancer-cell-invasion
#16
Jerry F Tien, Alborz Mazloomian, S-W Grace Cheng, Christopher S Hughes, Christalle C T Chow, Leanna T Canapi, Arusha Oloumi, Genny Trigo-Gonzalez, Ali Bashashati, James Xu, Vicky C-D Chang, Sohrab P Shah, Samuel Aparicio, Gregg B Morin
CDK12 (cyclin-dependent kinase 12) is a regulatory kinase with evolutionarily conserved roles in modulating transcription elongation. Recent tumor genome studies of breast and ovarian cancers highlighted recurrent CDK12 mutations, which have been shown to disrupt DNA repair in cell-based assays. In breast cancers, CDK12 is also frequently co-amplified with the HER2 (ERBB2) oncogene. The mechanisms underlying functions of CDK12 in general and in cancer remain poorly defined. Based on global analysis of mRNA transcripts in normal and breast cancer cell lines with and without CDK12 amplification, we demonstrate that CDK12 primarily regulates alternative last exon (ALE) splicing, a specialized subtype of alternative mRNA splicing, that is both gene- and cell type-specific...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334891/rad51-interconnects-between-dna-replication-dna-repair-and-immunity
#17
Souparno Bhattacharya, Kalayarasan Srinivasan, Salim Abdisalaam, Fengtao Su, Prithvi Raj, Igor Dozmorov, Ritu Mishra, Edward K Wakeland, Subroto Ghose, Shibani Mukherjee, Aroumougame Asaithamby
RAD51, a multifunctional protein, plays a central role in DNA replication and homologous recombination repair, and is known to be involved in cancer development. We identified a novel role for RAD51 in innate immune response signaling. Defects in RAD51 lead to the accumulation of self-DNA in the cytoplasm, triggering a STING-mediated innate immune response after replication stress and DNA damage. In the absence of RAD51, the unprotected newly replicated genome is degraded by the exonuclease activity of MRE11, and the fragmented nascent DNA accumulates in the cytosol, initiating an innate immune response...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334850/aicardi-gouti%C3%A3-res-syndrome-protein-trex1-suppresses-l1-and-maintains-genome-integrity-through-exonuclease-independent-orf1p-depletion
#18
Peng Li, Juan Du, John L Goodier, Jingwei Hou, Jian Kang, Haig H Kazazian, Ke Zhao, Xiao-Fang Yu
Maintaining genome integrity is important for cells and damaged DNA triggers autoimmunity. Previous studies have reported that Three-prime repair exonuclease 1(TREX1), an endogenous DNA exonuclease, prevents immune activation by depleting damaged DNA, thus preventing the development of certain autoimmune diseases. Consistently, mutations in TREX1 are linked with autoimmune diseases such as systemic lupus erythematosus, Aicardi-Goutières syndrome (AGS) and familial chilblain lupus. However, TREX1 mutants competent for DNA exonuclease activity are also linked to AGS...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334815/gcn5-mediated-rph1-acetylation-regulates-its-autophagic-degradation-under-dna-damage-stress
#19
Feng Li, Liang-De Zheng, Xin Chen, Xiaolu Zhao, Scott D Briggs, Hai-Ning Du
Histone modifiers regulate proper cellular activities in response to various environmental stress by modulating gene expression. In budding yeast, Rph1 transcriptionally represses many DNA damage or autophagy-related gene expression. However, little is known how Rph1 is regulated during these stress conditions. Here, we report that Rph1 is degraded upon DNA damage stress conditions. Notably, this degradation occurs via the autophagy pathway rather than through 26S proteasome proteolysis. Deletion of ATG genes or inhibition of vacuole protease activity compromises Rph1 turnover...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334742/recognition-but-no-repair-of-abasic-site-in-single-stranded-dna-by-human-ribosomal-us3-protein-residing-within-intact-40s-subunit
#20
Anastasia S Grosheva, Dmitry O Zharkov, Joachim Stahl, Alexander V Gopanenko, Alexey E Tupikin, Marsel R Kabilov, Dmitri M Graifer, Galina G Karpova
Isolated human ribosomal protein uS3 has extra-ribosomal functions including those related to base excision DNA repair, e.g. AP lyase activity that nicks double-stranded (ds) DNA 3΄ to the abasic (AP) site. However, the ability of uS3 residing within ribosome to recognize and cleave damaged DNA has never been addressed. Here, we compare interactions of single-stranded (ss) DNA and dsDNA bearing AP site with human ribosome-bound uS3 and with the isolated protein, whose interactions with ssDNA were not yet studied...
January 30, 2017: Nucleic Acids Research
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