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DNA DAMAGE AND REPAIR

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https://www.readbyqxmd.com/read/28938675/ape1-overexpression-is-associated-with-poor-survival-in-patients-with-solid-tumors-a-meta-analysis
#1
Chun-Ling Yuan, Fan He, Jia-Zhou Ye, Hui-Ni Wu, Jin-Yan Zhang, Zhi-Hui Liu, Yong-Qiang Li, Xiao-Ling Luo, Yan Lin, Rong Liang
APE1 is known as a key mediator of DNA damage repair pathways, and its clinical significance in different types of cancer is well studied. Herein, we performed a meta-analysis to determine the association of APE1 expression and survival in different types of solid cancer. We searched all eligible publications in PubMed, Web of Science and Embase platforms from inception to January 2017 and found 15 relevant manuscripts. Overall survival (OS), 12- and 36-month survival rates, and hazard ratios (HRs) were extracted and analyzed...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938540/microrna-128-3p-regulates-mitomycin-c-induced-dna-damage-response-in-lung-cancer-cells-through-repressing-sptan1
#2
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
#3
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/28937798/dual-effects-of-resveratrol-on-cell-death-and-proliferation-of-colon-cancer-cells
#4
Álvaro San Hipólito-Luengo, Antonio Alcaide, Mariella Ramos-González, Elena Cercas, Susana Vallejo, Alejandra Romero, Elena Talero, Carlos F Sánchez-Ferrer, Virginia Motilva, Concepción Peiró
Colorectal cancer remains a main cause of deaths worldwide, and novel agents are being searched to treat this disease. Polyphenols have emerged as promising therapeutic tools in cancer. Resveratrol (3,5,4'-trihydoxy-trans-stilbene) induces cell death in different tumor cell lines, and it also stimulates the proliferation of specific breast and prostate cancer cell lines. Here, we studied the impact of resveratrol over a 100-fold concentration range on cell death and proliferation of HT-29 colorectal adenocarcinoma cells...
September 22, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28937603/proteome-stability-as-a-key-factor-of-genome-integrity
#5
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/28937154/structural-basis-of-interstrand-cross-link-repair-by-o-6-alkylguanine-dna-alkyltransferase
#6
Alexey Y Denisov, Francis P McManus, Derek K O'Flaherty, Anne M Noronha, Christopher J Wilds
DNA interstrand cross-links (ICL) are among the most cytotoxic lesions found in biological systems. O(6)-Alkylguanine DNA alkyltransferases (AGTs) are capable of removing alkylation damage from the O(6)-atom of 2'-deoxyguanosine and the O(4)-atom of thymidine. Human AGT (hAGT) has demonstrated the ability to repair an interstrand cross-linked duplex where two O(6)-atoms of 2'-deoxyguanosine were tethered by a butylene (XLGG4) or heptylene (XLGG7) linkage. However, the analogous ICL between the O(4)-atoms of thymidine was found to evade repair...
September 22, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28936697/reactive-oxygen-species-and-glutathione-antioxidants-in-the-testis-of-the-soil-biosentinel-podarcis-sicula-rafinesque-1810
#7
Giulia Guerriero, Gerardino D'Errico, Rossella Di Giaimo, Dea Rabbito, Oladokun Sulaiman Olanrewaju, Gaetano Ciarcia
Important toxicological achievements have been made during the last decades using reptiles. We focus our investigation on gonadal reproductive health of the soil biosentinel Podarcis sicula which is very sensitive to endocrine-disrupting chemicals. The aim of this study is to quantitatively detect, by sensitive microassays, reactive oxygen species and the glutathione antioxidants in the testis and investigate if they are differentially expressed before and after remediation of a site of the "Land of Fires" (Campania, Italy) subject to illicit dumping of unknown material...
September 22, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28936205/homologous-recombination-in-protozoan-parasites-and-recombinase-inhibitors
#8
REVIEW
Andrew A Kelso, Sarah M Waldvogel, Adam J Luthman, Michael G Sehorn
Homologous recombination (HR) is a DNA double-strand break (DSB) repair pathway that utilizes a homologous template to fully repair the damaged DNA. HR is critical to maintain genome stability and to ensure genetic diversity during meiosis. A specialized class of enzymes known as recombinases facilitate the exchange of genetic information between sister chromatids or homologous chromosomes with the help of numerous protein accessory factors. The majority of the HR machinery is highly conserved among eukaryotes...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28935542/phase-i-trial-of-veliparib-a-poly-adp-ribose-polymerase-inhibitor-plus-metronomic-cyclophosphamide-in-metastatic-her2-negative-breast-cancer
#9
Jesus Anampa, Alice Chen, John Wright, Margi Patel, Christine Pellegrino, Karen Fehn, Joseph A Sparano, Eleni Andreopoulou
BACKGROUND: Poly-ADP-ribose-polymerase is an essential nuclear enzyme, involved in base-excision repair of damaged DNA. Poly-ADP-ribose-polymerase inhibition sensitizes tumor cells to cytotoxic agents, which induce DNA damage, including cyclophosphamide (C), and metronomic dosing of C may optimize potential for synergy. METHODS: The primary objective of this phase I trial was to determine the safety and identify the recommended phase II dose of the combination of low-dose oral C (50, 75, 100, and 125 mg) once daily in combination with veliparib (V) (100, 200, and 300 mg) administered twice a day (BID) for 21-day cycles using a standard 3 + 3 design in patients with metastatic human epidermal growth factor receptor 2/neu-negative breast cancer...
September 1, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28931330/sequential-molecular-changes-and-dynamic-oxidative-stress-in-high-grade-serous-ovarian-carcinogenesis
#10
Hiroshi Kobayashi, Kenji Ogawa, Naoki Kawahara, Kana Iwai, Emiko Niiro, Sachiko Morioka, Yuki Yamada
The mechanism of high-grade serous ovarian cancer (HGSC) development remains elusive. This review outlines recent advances in the understanding of sequential molecular changes associated with the development of HGSC, as well as describes oxidative stress-induced genomic instability and carcinogenesis. This article reviews the English-language literature between 2005 and 2017. Clinicopathological features analysis provide a sequential progression of fallopian tubal epithelium to precursor lesions to type 2 HGSC...
September 21, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28930988/application-of-laser-micro-irradiation-for-examination-of-single-and-double-strand-break-repair-in-mammalian-cells
#11
Nathaniel W Holton, Joel F Andrews, Natalie R Gassman
Highly coordinated DNA repair pathways exist to detect, excise and replace damaged DNA bases, and coordinate repair of DNA strand breaks. While molecular biology techniques have clarified structure, enzymatic functions, and kinetics of repair proteins, there is still a need to understand how repair is coordinated within the nucleus. Laser micro-irradiation offers a powerful tool for inducing DNA damage and monitoring the recruitment of repair proteins. Induction of DNA damage by laser micro-irradiation can occur with a range of wavelengths, and users can reliably induce single strand breaks, base lesions and double strand breaks with a range of doses...
September 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28930678/dna-ligase-iv-guides-end-processing-choice-during-nonhomologous-end-joining
#12
Michael P Conlin, Dylan A Reid, George W Small, Howard H Chang, Go Watanabe, Michael R Lieber, Dale A Ramsden, Eli Rothenberg
Nonhomologous end joining (NHEJ) must adapt to diverse end structures during repair of chromosome breaks. Here, we investigate the mechanistic basis for this flexibility. DNA ends are aligned in a paired-end complex (PEC) by Ku, XLF, XRCC4, and DNA ligase IV (LIG4); we show by single-molecule analysis how terminal mispairs lead to mobilization of ends within PECs and consequent sampling of more end-alignment configurations. This remodeling is essential for direct ligation of damaged and mispaired ends during cellular NHEJ, since remodeling and ligation of such ends both require a LIG4-specific structural motif, insert1...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930563/mass-spectrometry-based-proteomic-analysis-of-the-dna-damage-response
#13
Matthew P Stokes, Yiying Zhu, Charles L Farnsworth
In response to DNA damage, cells have evolved mechanisms to halt cell cycle progression, activate repair, or initiate apoptosis. These DNA damage response (DDR) pathways are critical for cellular survival in response to genomic insult, and play important roles in growth, development, and disease. Historically, mediators of DNA damage response signaling have been studied one or a few proteins at a time. Advances in mass spectrometry instrumentation and enrichment methods now allow for more global analysis of the DDR in cells and tissues...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28930533/53bp1-a-guardian-for-centrosomal-integrity
#14
Haeyoung Kim, Hyungshin Yim
53BP1 is known as a mediator in DNA damage response and a regulator of DNA double-stranded breaks (DSBs) repair. 53BP1 was recently reported to be a centrosomal protein and a binding partner of mitotic polo-like kinase 1 (Plk1). The stability of 53BP1, in response to DSBs, is regulated by its phosphorylation, deubiquitination, and ubiquitination. During mitosis, 53BP1 is stabilized by phosphorylation at S380, a putative binding region with polo-box domain of Plk1, and deubiquitination by ubiquitin-specific protease 7 (USP7)...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28928752/climate-clever-clovers-new-paradigm-to-reduce-the-environmental-footprint-of-ruminants-by-breeding-low-methanogenic-forages-utilizing-haplotype-variation
#15
Parwinder Kaur, Rudi Appels, Philipp E Bayer, Gabriel Keeble-Gagnere, Jiankang Wang, Hideki Hirakawa, Kenta Shirasawa, Philip Vercoe, Katia Stefanova, Zoey Durmic, Phillip Nichols, Clinton Revell, Sachiko N Isobe, David Edwards, William Erskine
Mitigating methane production by ruminants is a significant challenge to global livestock production. This research offers a new paradigm to reduce methane emissions from ruminants by breeding climate-clever clovers. We demonstrate wide genetic diversity for the trait methanogenic potential in Australia's key pasture legume, subterranean clover (Trifolium subterraneum L.). In a bi-parental population the broadsense heritability in methanogenic potential was moderate (H(2) = 0.4) and allelic variation in a region of Chr 8 accounted for 7...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28927723/antimutagenic-activity-of-vitamin-b1-against-damages-induced-by-chemical-and-physical-mutagens-in-salmonella-typhimurium-and-escherichia-coli
#16
Myriam Arriaga-Alba, Jaime Sánchez-Navarrete, Nancy Jannet Ruiz-Pérez, Julia Dolores Toscano-Garibay
Thiamine (vitamin B1) is an essential nutrient acting mainly as an enzymatic cofactor on diverse cell processes. It has been reported that vitamin B1 has a significant role in the signaling pathways related to the response to adverse environmental conditions (chemical and physical). The objectives of this study were to evaluate the antimutagenic potential of vitamin B1 in front of DNA-alkylating agents in the presence/absence of ogt and ada repairing genes in Salmonella typhimurium strains and against damage induced by ultraviolet light type C in Escherichia coli strains mutated at the uvrABC system and recBCD enzymes...
September 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28927013/transcription-factors-responding-to-pb-stress-in-maize
#17
Yanling Zhang, Fei Ge, Fengxia Hou, Wenting Sun, Qi Zheng, Xiaoxiang Zhang, Langlang Ma, Jun Fu, Xiujing He, Huanwei Peng, Guangtang Pan, Yaou Shen
Pb can damage the physiological function of human organs by entering the human body via food-chain enrichment. Revealing the mechanisms of maize tolerance to Pb is critical for preventing this. In this study, a Pb-tolerant maize inbred line, 178, was used to analyse transcription factors (TFs) expressed under Pb stress based on RNA sequencing data. A total of 464 genes expressed in control check (CK) or Pb treatment samples were annotated as TFs. Among them, 262 differentially expressed transcription factors (DETs) were identified that responded to Pb treatment...
September 18, 2017: Genes
https://www.readbyqxmd.com/read/28926637/selective-cytotoxicity-of-the-anti-diabetic-drug-metformin-in-glucose-deprived-chicken-dt40-cells
#18
Kei Kadoda, Takahito Moriwaki, Masataka Tsuda, Hiroyuki Sasanuma, Masamichi Ishiai, Minoru Takata, Hiroshi Ide, Shin-Ichiro Masunaga, Shunichi Takeda, Keizo Tano
Metformin is a biguanide drug that is widely used in the treatment of diabetes. Epidemiological studies have indicated that metformin exhibits anti-cancer activity. However, the molecular mechanisms underlying this activity currently remain unclear. We hypothesized that metformin is cytotoxic in a tumor-specific environment such as glucose deprivation and/or low oxygen (O2) tension. We herein demonstrated that metformin was highly cytotoxic under glucose-depleted, but not hypoxic (2% O2) conditions. In order to elucidate the underlying mechanisms of this selective cytotoxicity, we treated exposed DNA repair-deficient chicken DT40 cells with metformin under glucose-depleted conditions and measured cellular sensitivity...
2017: PloS One
https://www.readbyqxmd.com/read/28924389/structural-maintenance-of-chromosomes-protein-1-role-in-genome-stability-and-tumorigenesis
#19
REVIEW
Fei Yi, Zhuo Wang, Jingwei Liu, Ying Zhang, Zhijun Wang, Hongde Xu, Xiaoman Li, Ning Bai, Liu Cao, Xiaoyu Song
SMC1 (Structural Maintenance of Chromosomes protein 1), well known as one of the SMC superfamily members, has been explored to function in many activities including chromosome dynamics, cell cycle checkpoint, DNA damage repair and genome stability. Upon being properly assembled as part of cohesin, SMC1 can be phosphorylated by ATM and mediate downstream DNA damage repair after ionizing irradiation. Abnormal gene expression or mutation of SMC1 can cause defect in the DNA damage repair pathway, which has been strongly associated with tumorigenesis...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28923949/cytosine-deamination-and-base-excision-repair-cause-r-loop-induced-cag-repeat-fragility-and-instability-in-saccharomyces-cerevisiae
#20
Xiaofeng A Su, Catherine H Freudenreich
CAG/CTG repeats are structure-forming repetitive DNA sequences, and expansion beyond a threshold of ∼35 CAG repeats is the cause of several human diseases. Expanded CAG repeats are prone to breakage, and repair of the breaks can cause repeat contractions and expansions. In this study, we found that cotranscriptional R-loops formed at a CAG-70 repeat inserted into a yeast chromosome. R-loops were further elevated upon deletion of yeast RNaseH genes and caused repeat fragility. A significant increase in CAG repeat contractions was also observed, consistent with previous human cell studies...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
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