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https://www.readbyqxmd.com/read/28938540/microrna-128-3p-regulates-mitomycin-c-induced-dna-damage-response-in-lung-cancer-cells-through-repressing-sptan1
#1
Rui Zhang, Chang Liu, Yahan Niu, Ying Jing, Haiyang Zhang, Jin Wang, Jie Yang, Ke Zen, Junfeng Zhang, Chen-Yu Zhang, Donghai Li
The DNA damage response is critical for maintaining genome integrity and preventing damage to DNA due to endogenous and exogenous insults. Mitomycin C (MMC), a potent DNA cross-linker, is used as a chemotherapeutic agent because it causes DNA inter-strand cross-links (DNA ICLs) in cancer cells. While many microRNAs, which may serve as oncogenes or tumor suppressors, are grossly dysregulated in human cancers, little is known about their roles in MMC-treated lung cancer. Here, we report that miR-128-3p can attenuate repair of DNA ICLs by targeting SPTAN1 (αII Sp), resulting in cell cycle arrest and promoting chromosomal aberrations in lung cancer cells treated with MMC...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938088/small-molecule-inhibitors-targeting-dna-repair-and-dna-repair-deficiency-in-research-and-cancer-therapy
#2
REVIEW
Sarah R Hengel, M Ashley Spies, Maria Spies
To maintain stable genomes and to avoid cancer and aging, cells need to repair a multitude of deleterious DNA lesions, which arise constantly in every cell. Processes that support genome integrity in normal cells, however, allow cancer cells to develop resistance to radiation and DNA-damaging chemotherapeutics. Chemical inhibition of the key DNA repair proteins and pharmacologically induced synthetic lethality have become instrumental in both dissecting the complex DNA repair networks and as promising anticancer agents...
September 21, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28937603/proteome-stability-as-a-key-factor-of-genome-integrity
#3
REVIEW
Sentiljana Gumeni, Zoi Evangelakou, Vassilis G Gorgoulis, Ioannis P Trougakos
DNA damage is constantly produced by both endogenous and exogenous factors; DNA lesions then trigger the so-called DNA damaged response (DDR). This is a highly synchronized pathway that involves recognition, signaling and repair of the damage. Failure to eliminate DNA lesions is associated with genome instability, a driving force in tumorigenesis. Proteins carry out the vast majority of cellular functions and thus proteome quality control (PQC) is critical for the maintenance of cellular functionality. PQC is assured by the proteostasis network (PN), which under conditions of proteome instability address the triage decision of protein fold, hold, or degrade...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28936976/progress-in-studies-of-the-mechanisms-and-clinical-diagnosis-of-cervical-carcinoma-associated-with-genomic-integration-of-high-risk-human-papillomavirus-dna
#4
Sha-Sha Huang, Deng-Zai Hao, Yan Zhang, Hou-Ming Liu, Wan-Shui Shan
High-risk human papillomavirus (hrHPV) has been identified as a key factor in the development of cervical cancer. Integration of viral DNA into the host genome has been postulated as an important etiological event during cervical carcinogenesis. High-risk HPV DNA integration frequently results in either the deletion or interruption of the large fragment of E1 and E2 region and the overexpression of oncogenes E6 and E7 in the viral genome, and the activation of oncogenes and the inactivation of tumor suppressors in host genome...
September 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28935922/arabidopsis-r1r2r3-myb-proteins-are-essential-for-inhibiting-cell-division-in-response-to-dna-damage
#5
Poyu Chen, Hirotomo Takatsuka, Naoki Takahashi, Rie Kurata, Yoichiro Fukao, Kosuke Kobayashi, Masaki Ito, Masaaki Umeda
Inhibition of cell division is an active response to DNA damage that enables cells to maintain genome integrity. However, how DNA damage arrests the plant cell cycle is largely unknown. Here, we show that the repressor-type R1R2R3-Myb transcription factors (Rep-MYBs), which suppress G2/M-specific genes, are required to inhibit cell division in response to DNA damage. Knockout mutants are resistant to agents that cause DNA double-strand breaks and replication stress. Cyclin-dependent kinases (CDKs) can phosphorylate Rep-MYBs in vitro and are involved in their proteasomal degradation...
September 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28931206/metabolic-engineering-a-yeast-to-produce-astaxanthin
#6
Yu-Ju Lin, Jui-Jen Chang, Hao-Yeh Lin, Caroline Thia, Yi-Ying Kao, Chieh-Chen Huang, Wen-Hsiung Li
In this study, an astaxanthin-biosynthesis Kluyveromyces marxianus strain Sm23 was first constructed, which could produce 31µg/g DCW astaxanthin. Then, repeated genome integration of the key astaxanthin biosynthesis genes Hpchyb and bkt was done to increase gene copy number and astaxanthin yield. Four improved strains were obtained and the yield of astaxanthin and the total yield of carotenoids in a strain increased with the copy numbers of Hpchyb and bkt. To improve the yield further, the gene Hpchyb from Haematococcus pluvialis was modified by site-directed mutagenesis to increase the enzyme efficiency or/and to prevent the heterologous protein degradation by ubiquitination...
July 23, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28927196/the-intricate-interplay-between-msi-and-polymorphisms-of-dna-repair-enzymes-in-gastric-cancer-h-pylori-associated
#7
Isabelle Joyce de Lima Silva-Fernandes, Emanuele Silva de Oliveira, Juliana Carvalho Santos, Marcelo Lima Ribeiro, Adriana Camargo Ferrasi, Maria Inês de Moura Campos Pardini, Rommel Mário Rodriguez Burbano, Silvia Helena Barem Rabenhorst
Gastric cancer is the fourth most common type of cancer worldwide. Helicobacter pylori is a well-established risk factor and may cause injuries to genomic integrity through an inefficient DNA repair. This study aimed to examine the influence of polymorphisms in DNA repair enzymes using markers for microsatellite instability (MSI). Polymorphisms of DNA repair enzymes were detected by PCR-RFLP and MSI, by high resolution melt (HRM) analysis. Helicobacter pylori detection and genotyping were accomplished by PCR...
July 1, 2017: Mutagenesis
https://www.readbyqxmd.com/read/28925362/generation-of-a-klf15-homozygous-knockout-human-embryonic-stem-cell-line-using-paired-crispr-cas9n-and-human-cardiomyocytes-derivation
#8
Claudia Noack, Luis Peter Haupt, Wolfram-Hubertus Zimmermann, Katrin Streckfuss-Bömeke, Laura Cecilia Zelarayán
Krueppel-like factor 15 (KLF15) is abundantly expressed in liver, kidney, and muscle, including myocardium. In the adult heart KLF15 is important to maintain homeostasis and to repress hypertrophic remodeling. We generated a homozygous hESC KLF15 knockout (KO) line using paired CRISPR/Cas9n. KLF15-KO cells maintained full pluripotency and differentiation potential as well as genomic integrity. We demonstrated that KLF15-KO cells can be differentiated into morphologically normal cardiomyocytes turning them into a valuable tool for studying human KLF15-mediated mechanisms resulting in human cardiac dysfunction...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28922417/lingering-single-strand-breaks-trigger-rad51-independent-homology-directed-repair-of-collapsed-replication-forks-in-the-polynucleotide-kinase-phosphatase-mutant-of-fission-yeast
#9
Arancha Sanchez, Mariana C Gadaleta, Oliver Limbo, Paul Russell
The DNA repair enzyme polynucleotide kinase/phosphatase (PNKP) protects genome integrity by restoring ligatable 5'-phosphate and 3'-hydroxyl termini at single-strand breaks (SSBs). In humans, PNKP mutations underlie the neurological disease known as MCSZ, but these individuals are not predisposed for cancer, implying effective alternative repair pathways in dividing cells. Homology-directed repair (HDR) of collapsed replication forks was proposed to repair SSBs in PNKP-deficient cells, but the critical HDR protein Rad51 is not required in PNKP-null (pnk1Δ) cells of Schizosaccharomyces pombe...
September 18, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28921472/telomere-damage-response-and-low-grade-inflammation
#10
Lihui Wang, Xianhua Yu, Jun-Ping Liu
Telomeres at the ends of chromosomes safeguard genome integrity and stability in human nucleated cells. However, telomere repeats shed off during cell proliferation and other stress responses. Our recent studies show that telomere attrition induces not only epithelial stem cell senescence but also low-grade inflammation in the lungs. The senescence-associated low-grade inflammation (SALI) is characteristic of alveolar stem cell replicative senescence, increased proinflammatory and anti-inflammatory cytokines, infiltrated immune cells, and spillover effects...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28919745/dose-and-time-effect-of-cdte-quantum-dots-on-antioxidant-capacities-of-the-liver-and-kidneys-in-mice
#11
Jilong Wang, Hubo Sun, Peijun Meng, Mengmeng Wang, Mi Tian, Yamin Xiong, Xueying Zhang, Peili Huang
Although quantum dot (QD)-induced toxicity occurs due to free radicals, generation of oxidative stress mediated by reactive oxygen species (ROS) formation is considered an important mechanism. However, free radical mechanisms are essentially difficult to elucidate at the molecular level because most biologically relevant free radicals are highly reactive and short-lived, making them difficult to directly detect, especially in vivo. Antioxidants play an important role in preventing or, in most cases, limiting the damage caused by ROS...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28912341/the-role-of-blm-helicase-in-homologous-recombination-gene-conversion-tract-length-and-recombination-between-diverged-sequences-in-drosophila
#12
Henry A Ertl, Daniel P Russo, Noori Srivastava, Joseph T Brooks, Thu N Dao, Jeannine R LaRocque
DNA double-strand breaks (DSBs) are a particularly deleterious class of DNA damage that threatens genome integrity. DSBs are repaired by three pathways: non-homologous end joining (NHEJ), homologous recombination (HR), and single-strand annealing (SSA). Drosophila melanogaster Blm (DmBlm) is the ortholog of Saccharomyces cerevisiae SGS1 and human BLM, and has been shown to suppress crossovers in mitotic cells and repair mitotic DNA gaps via HR. To further elucidate the role of DmBlm in repair of a simple DSB, and in particular recombination mechanisms, we utilized the DR-white and DR-white...
September 14, 2017: Genetics
https://www.readbyqxmd.com/read/28912125/blm-helicase-regulates-dna-repair-by-counteracting-rad51-loading-at-dna-double-strand-break-sites
#13
Dharm S Patel, Sarah M Misenko, Joonyoung Her, Samuel F Bunting
The BLM gene product, BLM, is a RECQ helicase that is involved in DNA replication and repair of DNA double-strand breaks by the homologous recombination (HR) pathway. During HR, BLM has both pro- and anti-recombinogenic activities, either of which may contribute to maintenance of genomic integrity. We find that in cells expressing a mutant version of BRCA1, an essential HR factor, ablation of BLM rescues genomic integrity and cell survival in the presence of DNA double-strand breaks. Improved genomic integrity in these cells is linked to a substantial increase in the stability of RAD51 at DNA double-strand break sites and in the overall efficiency of HR...
September 14, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28911331/dynamic-dna-methylation-reconfiguration-during-seed-development-and-germination
#14
Taiji Kawakatsu, Joseph R Nery, Rosa Castanon, Joseph R Ecker
BACKGROUND: Unlike animals, plants can pause their life cycle as dormant seeds. In both plants and animals, DNA methylation is involved in the regulation of gene expression and genome integrity. In animals, reprogramming erases and re-establishes DNA methylation during development. However, knowledge of reprogramming or reconfiguration in plants has been limited to pollen and the central cell. To better understand epigenetic reconfiguration in the embryo, which forms the plant body, we compared time-series methylomes of dry and germinating seeds to publicly available seed development methylomes...
September 15, 2017: Genome Biology
https://www.readbyqxmd.com/read/28911120/phirex-a-programmable-and-red-light-regulated-protein-expression-switch-for-yeast
#15
Lena Hochrein, Fabian Machens, Katrin Messerschmidt, Bernd Mueller-Roeber
Highly regulated induction systems enabling dose-dependent and reversible fine-tuning of protein expression output are beneficial for engineering complex biosynthetic pathways. To address this, we developed PhiReX, a novel red/far-red light-regulated protein expression system for use in Saccharomyces cerevisiae. PhiReX is based on the combination of a customizable synTALE DNA-binding domain, the VP64 activation domain and the light-sensitive dimerization of the photoreceptor PhyB and its interacting partner PIF3 from Arabidopsis thaliana...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28910492/p53-mediated-regulation-of-bile-acid-disposition-attenuates-cholic-acid-induced-cholestasis-in-mice
#16
Pan Chen, Dongshun Li, Yixin Chen, Jiahong Sun, Kaili Fu, Lihuan Guan, Huizhen Zhang, Yiming Jiang, Xi Li, Xuezhen Zeng, Xiao Chen, Min Huang, Huichang Bi
BACKGROUND AND PURPOSE: Tumor suppressor p53 is traditionally recognized as a surveillance molecule to preserve genome integrity. Recent studies have emerged on discovering its functions in metabolic diseases. Here we investigated the role of p53 in the regulation bile acid disposition and cholestasis. EXPERIMENTAL APPROACH: Bile acid disposition related gene expression profile altered by p53 activation was assessed in mouse primary hepatocytes with p53 depletion and in Trp53-null mice...
September 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28903896/the-regulatory-functions-of-pirna-piwi-in-spermatogenesis
#17
Zhi-Heng Yuan, Yan-Mei Zhao
A class of 24-32 nt PIWI-binding small noncoding RNAs (sncRNAs) termed as PIWI-interacting RNAs (piRNAs) have been identified in animal germline. Recent studies suggest that piRNA/PIWI pathway plays a critical role in both silencing of transposons and posttranscriptional regulation of mRNAs in animal germline. A study from Dr. Mofang Liu's lab in Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, reveals the physiological and pathological importance of PIWI metabolism (mouse PIWI as known as MIWI; human PIWI as HIWI) in mammalian spermatogenesis...
August 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28903076/role-of-human-dna2-hdna2-as-a-potential-target-for-cancer-and-other-diseases-a-systematic-review
#18
REVIEW
Pan-Pan Jia, Muhammad Junaid, Yan-Bo Ma, Farooq Ahmad, Yong-Fang Jia, Wei-Guo Li, De-Sheng Pei
DNA nuclease/helicase 2 (DNA2), a multi-functional protein protecting the high fidelity of genomic transmission, plays critical roles in DNA replication and repair processes. In the maturation of Okazaki fragments, DNA2 acts synergistically with other enzymes to cleave the DNA-RNA primer flaps via different pathways. DNA2 is also involved in the stability of mitochondrial DNA and the maintenance of telomeres. Moreover, DNA2 potentially participates in controlling the cell cycle by repairing the DNA replication faults at main checkpoints...
September 6, 2017: DNA Repair
https://www.readbyqxmd.com/read/28903034/piwi-is-required-to-limit-exhaustion-of-aging-somatic-stem-cells
#19
Pedro Sousa-Victor, Arshad Ayyaz, Rippei Hayashi, Yanyan Qi, David T Madden, Victoria V Lunyak, Heinrich Jasper
Sophisticated mechanisms that preserve genome integrity are critical to ensure the maintenance of regenerative capacity while preventing transformation of somatic stem cells (SCs), yet little is known about mechanisms regulating genome maintenance in these cells. Here, we show that intestinal stem cells (ISCs) induce the Argonaute family protein Piwi in response to JAK/STAT signaling during acute proliferative episodes. Piwi function is critical to ensure heterochromatin maintenance, suppress retrotransposon activation, and prevent DNA damage in homeostasis and under regenerative pressure...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28902877/purification-and-characterization-of-a-highly-specific-polyclonal-antibody-against-human-extracellular-signal-regulated-kinase-8-and-its-detection-in-lung-cancer
#20
Na-Li Cai, Andy T Y Lau, Fei-Yuan Yu, Dan-Dan Wu, Li-Juan Dai, Hai-Ying Mo, Chang-Min Lin, Yan-Ming Xu
Extracellular signal-regulated kinase 8 (ERK8), proposed as a novel potential therapeutic target for cancer, has been implicated in cell transformation, apoptosis, the protection of genomic integrity, and autophagy. To facilitate ERK8 research, a highly specific anti-ERK8 antibody is needed. In this article, we use the Immune Epitope Database and Analysis Resource online tool to predict B-cell epitopes of human ERK8 protein, and choose a 28 aa-peptide sequence to generate the GST-ERK8(28aa) fusion protein as the antigen for developing polyclonal antibody against ERK8...
2017: PloS One
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