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DNA DAMAGE AND REPAIR

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https://www.readbyqxmd.com/read/28806503/identification-of-the-dimer-exchange-interface-of-the-bacterial-dna-damage-response-protein-umud
#1
David A Murison, Rebecca C Timson, Bilyana Koleva, Michael Ordazzo, Penny J Beuning
The Escherichia coli SOS response, an induced DNA damage response pathway, confers survival on bacterial cells by providing accurate repair mechanisms as well as the potentially mutagenic pathway translesion synthesis (TLS). The umuD gene products are upregulated after DNA damage and play roles in both non-mutagenic and mutagenic aspects of the SOS response. Full-length UmuD is expressed as a homodimer of 139-amino-acid subunits, which eventually cleaves its N-terminal 24 amino acids to form UmuD'. The cleavage product, UmuD', together with UmuC, form the Y-family polymerase DNA Pol V (UmuD'2C) capable of performing TLS...
August 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28806395/rad6-promotes-dna-repair-and-stem-cell-signaling-in-ovarian-cancer-and-is-a-promising-therapeutic-target-to-prevent-and-treat-acquired-chemoresistance
#2
R R Somasagara, S M Spencer, K Tripathi, D W Clark, C Mani, L Madeira da Silva, J Scalici, H Kothayer, A D Westwell, R P Rocconi, K Palle
Ovarian cancer (OC) is the most deadly gynecological cancer and unlike most other neoplasms, survival rates for OC have not significantly improved in recent decades. We show that RAD6, an ubiquitin-conjugating enzyme, is significantly overexpressed in ovarian tumors and its expression increases in response to carboplatin chemotherapy. RAD6 expression correlated strongly with acquired chemoresistance and malignant behavior of OC cells, expression of stem cell genes and poor prognosis of OC patients, suggesting an important role for RAD6 in ovarian tumor progression...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28805830/in-vitro-and-in-vivo-analysis-of-visible-light-crosslinkable-gelatin-methacryloyl-gelma-hydrogels
#3
Iman Noshadi, Seonki Hong, Kelly E Sullivan, Ehsan Shirzaei Sani, Roberto Portillo-Lara, Ali Tamayol, Su Ryon Shin, Albert E Gao, Whitney L Stoppel, Lauren D Black Iii, Ali Khademhosseini, Nasim Annabi
Photocrosslinkable materials have been frequently used for constructing soft and biomimetic hydrogels for tissue engineering. Although ultraviolet (UV) light is commonly used for photocrosslinking such materials, its use has been associated with several biosafety concerns such as DNA damage, accelerated aging of tissues, and cancer. Here we report an injectable visible light crosslinked gelatin-based hydrogel for myocardium regeneration. Mechanical characterization revealed that the compressive moduli of the engineered hydrogels could be tuned in the range of 5-56 kPa by changing the concentrations of the initiator, co-initiator and co-monomer in the precursor formulation...
August 14, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28804543/light-of-dna-alkylating-agents-in-castration-resistant-prostate-cancer-cells-a-novel-mixed-egfr-dna-targeting-combi-molecule
#4
Guan-Can Liang, Hao-Feng Zheng, Yan-Xiong Chen, Teng-Cheng Li, Wei Liu, You-Qiang Fang
OBJECTIVE: The mechanism underlying the therapeutic effects of combi-molecule JDF12 on prostate cancer (PCa) DU145 cells remains still unclear. This study aimed to investigate the proteomic profile after JDF12 treatment in DU145 cells by comparing with that in Iressa treated cells and untreated cells. METHODS: MTT was used to evaluate drug cytotoxicity, DAPI staining was done to assess apoptosis of cells, and flow cytometry was used to analyze cell cycle. iTRAQ and qPCR were employed to obtain the proteomic profiles of JDF12 treated, Iressa treated, and untreated DU145 cells, and validate the expression of selected differentially expressed proteins, respectively...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28802828/photolyase-dynamics-and-electron-transfer-mechanisms-of-dna-repair
#5
REVIEW
Meng Zhang, Lijuan Wang, Dongping Zhong
Photolyase, a flavoenzyme containing flavin adenine dinucleotide (FAD) molecule as a catalytic cofactor, repairs UV-induced DNA damage of cyclobutane pyrimidine dimer (CPD) and pyrimidine-pyrimidone (6-4) photoproduct using blue light. The FAD cofactor, conserved in the whole protein superfamily of photolyase/cryptochromes, adopts a unique folded configuration at the active site that plays a critical functional role in DNA repair. Here, we review our comprehensive characterization of the dynamics of flavin cofactor and its repair photocycles by different classes of photolyases on the most fundamental level...
August 9, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28802254/tdp1-is-critical-for-the-repair-of-dna-breaks-induced-by-sapacitabine-a-nucleoside-also-targeting-atm-and-brca-deficient-tumors
#6
Muthana Al Abo, Hiroyuki Sasanuma, Xiaojun Liu, Vinodh N Rajapakse, Shar-Yin N Huang, Evgeny Kiselev, Shunichi Takeda, William Plunkett, Yves Pommier
2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine (CNDAC) is the active metabolite of the anticancer drug, sapacitabine. CNDAC is incorporated into the genome during DNA replication and subsequently undergoes beta-elimination that generates single-strand breaks with abnormal 3'-ends. Because tyrosyl-DNA phosphodiesterase 1 (TDP1) selectively hydrolyzes non-phosphorylated 3'-blocking ends, we tested its role in the repair of CNDAC-induced DNA damage. We show that cells lacking TDP1 (avian TDP1-/- DT40 cells and human TDP1 KO TSCER2 and HCT116 cells) exhibit marked hypersensitivity to CNDAC...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28801308/egfr-mutations-compromise-hypoxia-associated-radiation-resistance-through-impaired-replication-fork-associated-dna-damage-repair
#7
Mohammad Saki, Haruhiko Makino, Prashanthi Javvadi, Nozomi Tomimatsu, Lianghao Ding, Jennifer E Clark, Elaine Gavin, Kenichi Takeda, Joel Andrews, Debabrata Saha, Michael D Story, Sandeep Burma, Chaitanya Nirodi
Epidermal growth factor receptor (EGFR) signaling has been implicated in hypoxia-associated resistance to radiation or chemotherapy. Non-small cell lung carcinomas (NSCLC) with activating L858R or ΔE746-E750 EGFR mutations exhibit elevated EGFR activity and downstream signaling. Here, relative to wild type (WT) EGFR, mutant (MT) EGFR expression significantly increases radiosensitivity in hypoxic cells. Gene expression profiling in human bronchial epithelial cells (HBEC) revealed that MT-EGFR expression elevated transcripts related to cell cycle and replication in aerobic and hypoxic conditions and down-regulated RAD50, a critical component of non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA repair pathways...
August 11, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28800961/functional-consequences-of-inducible-genetic-elements-from-the-p53-sos-response-in-a-mammalian-organ-system
#8
O'neil W Guthrie
In response to DNA damage from ultraviolet (UV) radiation, bacteria deploy the SOS response in order to limit cell death. This bacterial SOS response is characterized by an increase in the recA gene that transactivates expression of multiple DNA repair genes. The current series of experiments demonstrate that a mammalian organ system (the cochlea) that is not evolutionarily conditioned to UV radiation can elicit SOS responses that are reminiscent of that of bacteria. This mammalian SOS response is characterized by an increase in the p53 gene with activation of multiple DNA repair genes that harbor p53 response elements in their promoters...
August 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28800752/a-type-i-combi-targeting-approach-for-the-design-of-molecules-with-enhanced-potency-against-brca1-2-mutant-and-o6-methylguanine-dna-methyltransferase-mgmt-expressing-tumour-cells
#9
Zhor Senhaji Mouhri, Elliot Goodfellow, Bertrand Jean-Claude
BACKGROUND: Mutations of the DNA repair proteins BRCA1/2 are synthetically lethal with the DNA repair enzyme poly(ADP-ribose) polymerase (PARP), which when inhibited, leads to cell death due to the absence of compensatory DNA repair mechanism. The potency of PARP inhibitors has now been clinically proven. However, disappointingly, acquired resistance mediated by the reactivation of wild type BRCA1/2 has been reported. In order to improve their efficacy, trials are ongoing to explore their combinations with temozolomide (TMZ)...
August 11, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28800532/cell-cycle-arrest-mediated-by-cd-induced-dna-damage-in-arabidopsis-root-tips
#10
Weina Cui, Hetong Wang, Jie Song, Xia Cao, Hilary J Rogers, Dennis Francis, Chunyun Jia, Lizong Sun, Meifang Hou, Yuesuo Yang, Peidong Tai, Wan Liu
Accumulating evidence demonstrates that the aberrant expression of cell cycle regulation and DNA repair genes can result in abnormal cell proliferation and genomic instability in eukaryotic cells under different stresses. Herein, Arabidopsis thaliana (Arabidopsis) seedlings were grown hydroponically on 0.5 × MS media containing cadmium (Cd) at 0-2.5mgL(-1) for 5d of treatment. Real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis revealed that expression of DNA damage repair and cell cycle regulation genes, including BRCA1, MRE11, WEE1, CDKA;1 and PCNA1, showed an inverted U-shaped dose-response...
August 8, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28799445/molecular-efficacy-of-radio-and-chemotherapy-sequences-from-direct-dna-damages-measurements
#11
Yanfang Dong, Yunfeng Chen, Limei Zhou, Yu Shao, Xianzhi Fu, Yi Zheng
PURPOSE: To investigate the molecular aspects of the synergy of between ionizing radiation and platinum (Pt) chemotherapeutic agents in cancer treatment with chemoradiation therapy (CRT), by measuring damages induced by low-energy electrons (LEE) to DNA bound to cisplatin. LEE are produced abundantly by any types of ionizing radiation and cisplatin represents a typical Pt-chemotherapeutic agents. MATERIALS AND METHODS: Our strategy involves two parallel administrations of cisplatin and irradiation with a 4...
August 11, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28799406/a-polymorphic-ggc-repeat-in-the-npas2-gene-and-its-association-with-melanoma
#12
Alessandra Franzoni, Elitza Markova-Car, Sanja Dević-Pavlić, Davor Jurišić, Cinzia Puppin, Catia Mio, Marila De Luca, Giulia Petruz, Giuseppe Damante, Sandra Kraljević Pavelić
Circadian clock regulation in mammals is controlled by feedback loops of a set of circadian genes. One of these circadian genes, NPAS2, encodes for a member of the bHLH-PAS class of transcription factors and is expressed in the forebrain and in some peripheral organs such as liver and skin. Other biological processes are also regulated by circadian genes. For example, NPAS2 is involved in cell proliferation, DNA damage repair and malignant transformation. Aberrant expression of clock genes has been previously observed in melanoma which led to our effort to sequence the NPAS2 promoter region in this cancer type...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28798731/mechanisms-and-regulation-of-extracellular-dna-release-and-its-biological-roles-in-microbial-communities
#13
REVIEW
Alejandra L Ibáñez de Aldecoa, Olga Zafra, José E González-Pastor
The capacity to release genetic material into the extracellular medium has been reported in cultures of numerous species of bacteria, archaea, and fungi, and also in the context of multicellular microbial communities such as biofilms. Moreover, extracellular DNA (eDNA) of microbial origin is widespread in natural aquatic and terrestrial environments. Different specific mechanisms are involved in eDNA release, such as autolysis and active secretion, as well as through its association with membrane vesicles. It is noteworthy that in microorganisms, in which DNA release has been studied in detail, the production of eDNA is coordinated by the population when it reaches a certain cell density, and is induced in a subpopulation in response to the accumulation of quorum sensing signals...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28798238/molecular-mechanisms-and-genomic-maps-of-dna-excision-repair-in-e-coli-and-humans
#14
Jinchuan Hu, Christopher P Selby, Sheera Adar, Ogun Adebali, Aziz Sancar
Nucleotide excision repair is a major DNA repair mechanism in all cellular organisms. In this repair system the DNA damage is removed by concerted dual incisions bracketing the damage and at precise distance from the damage. Here, we review the basic mechanisms of excision repair in E.coli and humans and the recent genome-wide mapping of DNA damage and repair in these organisms at single-nucleotide resolution.
August 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28797905/evidence-for-the-role-of-bmnpv-bm65-protein-in-the-repair-of-ultraviolet-induced-dna-damage
#15
Qi Tang, Peng Wu, Zhaoyang Hu, Yanhua Yang, Lipeng Qiu, Hanqing Liu, Shanying Zhu, Zhongjian Guo, Hengchuan Xia, Keping Chen, Guohui Li
It is unclear how, or to what extent, baculovirus DNA that has been damaged by ultraviolet (UV) light is repaired during infection and replication. In our previous study, expression of Bombyx mori nucleopolyhedrovirus (BmNPV) ORF Bm65, a homolog of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac79, correlated with decreased inactivation of virus by UV irradiation. In the current study, we accumulated more evidence pointing to a role for Bm65 in repair of UV-induced DNA damage. The localization of Bm65 was studied using enhanced green fluorescent protein (EGFP) fusion constructs expressed in BmN cells transfected with a Bm65 expression plasmid...
August 8, 2017: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/28797855/exploring-genetic-attributions-underlying-radiotherapy-induced-fatigue-in-prostate-cancer-patients
#16
Sepehr Hashemi, Juan Luis Fernandez Martinez, Leorey Saligan, Stephen Sonis
CONTEXT: Despite numerous proposed mechanisms, no definitive pathophysiology underlying Radiotherapy-Induced Fatigue (RIF) has been established. However, the dysregulation of a set of 35 genes was recently validated to predict development of fatigue in prostate cancer patients (PCP's) receiving radiotherapy. OBJECTIVES: To hypothesize novel pathways, and provide genetic targets for currently proposed pathways implicated in RIF development through analysis of the previously validated gene set...
August 7, 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28797568/the-combination-of-a-966492-and-topotecan-for-effective-radiosensitization-on-glioblastoma-spheroids
#17
Fereshteh Koosha, Ali Neshasteh-Riz, Abbas Takavar, Nazila Eyvazzadeh, Zohreh Mazaheri, Samira Eynali, Mehdi Mousavi
Radiotherapy is one of the modalities in the treatment of glioblastoma patients, but glioma tumors are resistant to radiation and also chemotherapy drugs. Thus, researchers are investigating drugs which have radiosensitization capabilities in order to improve radiotherapy. PARP enzymes and topoisomerase I enzymes have a critical role in repairing DNA damage in tumor cells. Thus, inhibiting activity of these enzymes helps stop DNA damage repair and increase DSB lethal damages. In the current study, we investigated the combination of TPT as a topoisomerase I inhibitor, and A-966492 as a novel PARP inhibitor for further radiosensitization...
August 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28796599/reversing-adp-ribosylation
#18
Giuliana Katharina Moeller, Gyula Timinszky
The modification of serines by molecules of ADP-ribose plays an important role in signaling that the DNA in a cell has been damaged and needs to be repaired.
August 10, 2017: ELife
https://www.readbyqxmd.com/read/28796249/rho-inhibition-by-lovastatin-affects-apoptosis-and-dsb-repair-of-primary-human-lung-cells-in-vitro-and-lung-tissue-in-vivo-following-fractionated-irradiation
#19
Verena Ziegler, Christian Henninger, Ioannis Simiantonakis, Marcel Buchholzer, Mohammad Reza Ahmadian, Wilfried Budach, Gerhard Fritz
Thoracic radiotherapy causes damage of normal lung tissue, which limits the cumulative radiation dose and, hence, confines the anticancer efficacy of radiotherapy and impacts the quality of life of tumor patients. Ras-homologous (Rho) small GTPases regulate multiple stress responses and cell death. Therefore, we investigated whether pharmacological targeting of Rho signaling by the HMG-CoA-reductase inhibitor lovastatin influences ionizing radiation (IR)-induced toxicity in primary human lung fibroblasts, lung epithelial and lung microvascular endothelial cells in vitro and subchronic mouse lung tissue damage following hypo-fractionated irradiation (4x4 Gy)...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28796034/the-association-between-xpg-polymorphisms-and-cancer-susceptibility-evidence-from-observational-studies
#20
Cuihong Han, Xiaoyi Huang, Ruixi Hua, Shujie Song, Lihua Lyu, Na Ta, Jinhong Zhu, Peixi Zhang
BACKGROUND: Exposure to environmental carcinogens can cause damages to DNA. If not properly repaired, the DNA damages may increase the risk of carcinogenesis. Xeroderma pigmentosum group G (XPG) gene is an essential gene in the nucleotide excision repair (NER) pathway. The association between XPG polymorphisms and cancer susceptibility has been the focus of attention in the molecular epidemiology of cancer. However, the conclusions have been divergent. Therefore, we conducted a comprehensive meta-analysis to precisely evaluate the association of 3 frequently investigated XPG polymorphisms (rs751402, rs873601, and rs2296147) with cancer risk...
August 2017: Medicine (Baltimore)
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