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https://www.readbyqxmd.com/read/28903076/role-of-human-dna2-hdna2-as-a-potential-target-for-cancer-and-other-diseases-a-systematic-review
#1
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/28892740/human-ogg1-activity-in-nucleosomes-is-facilitated-by-transient-unwrapping-of-dna-and-is-influenced-by-the-local-histone-environment
#2
Katharina Bilotti, Erin E Kennedy, Chuxuan Li, Sarah Delaney
If unrepaired, damage to genomic DNA can cause mutations and/or be cytotoxic. Single base lesions are repaired via the base excision repair (BER) pathway. The first step in BER is the recognition and removal of the nucleobase lesion by a glycosylase enzyme. For example, human oxoguanine glycosylase 1 (hOGG1) is responsible for removal of the prototypic oxidatively damaged nucleobase, 8-oxo-7,8-dihydroguanine (8-oxoG). To date, most studies of glycosylases have used free duplex DNA substrates. However, cellular DNA is packaged as repeating nucleosome units, with 145 base pair segments of DNA wrapped around histone protein octamers...
September 1, 2017: DNA Repair
https://www.readbyqxmd.com/read/28887667/ape1-modulates-cellular-responses-to-organophosphate-pesticide-induced-oxidative-damage-in-non-small-cell-lung-carcinoma-a549-cells
#3
Shweta Thakur, Monisha Dhiman, Anil K Mantha
Monocrotophos (MCP) and chlorpyrifos (CP) are widely used organophosphate pesticides (OPPs), speculated to be linked with human pathologies including cancer. Owing to the fact that lung cells are most vulnerable to the environmental toxins, the development and progression of lung cancer can be caused by the exposure of OPPs. The present study investigates the oxidative DNA damage response evoked by MCP and CP in human non-small cell lung carcinoma A549 cells. A549 cells were exposed to MCP and CP; cytotoxicity and reactive oxygen species (ROS) generation were measured to select the non-toxic dose...
September 8, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28886188/alkylation-induced-cerebellar-degeneration-dependent-on-aag-and-parp1-does-not-occur-via-previously-established-cell-death-mechanisms
#4
Carrie M Margulies, Isaac Alexander Chaim, Aprotim Mazumder, June Criscione, Leona D Samson
Alkylating agents are ubiquitous in our internal and external environments, causing DNA damage that contributes to mutations and cell death that can result in aging, tissue degeneration and cancer. Repair of methylated DNA bases occurs primarily through the base excision repair (BER) pathway, a multi-enzyme pathway initiated by the alkyladenine DNA glycosylase (Aag, also known as Mpg). Previous work demonstrated that mice treated with the alkylating agent methyl methanesulfonate (MMS) undergo cerebellar degeneration in an Aag-dependent manner, whereby increased BER initiation by Aag causes increased tissue damage that is dependent on activation of poly (ADP-ribose) polymerase 1 (Parp1)...
2017: PloS One
https://www.readbyqxmd.com/read/28861684/curcumin-revitalizes-amyloid-beta-25-35-induced-and-organophosphate-pesticides-pestered-neurotoxicity-in-sh-sy5y-and-imr-32-cells-via-activation-of-ape1-and-nrf2
#5
Bibekananda Sarkar, Monisha Dhiman, Sunil Mittal, Anil K Mantha
Amyloid beta (Aβ) peptide deposition is the primary cause of neurodegeneration in Alzheimer's disease (AD) pathogenesis. Several reports point towards the role of pesticides in the AD pathogenesis, especially organophosphate pesticides (OPPs). Monocrotophos (MCP) and Chlorpyrifos (CP) are the most widely used OPPs. In this study, the role of MCP and CP in augmenting the Aβ-induced oxidative stress associated with the neurodegeneration in AD has been assessed in human neuroblastoma IMR-32 and SH-SY5Y cell lines...
August 31, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28846606/the-emerging-role-of-glp-1-receptors-in-dna-repair-implications-in-neurological-disorders
#6
REVIEW
Jenq-Lin Yang, Wei-Yu Chen, Shang-Der Chen
Glucagon-like peptide-1 (GLP-1) is originally found as a metabolic hormone (incretin) that is able to regulate blood-glucose levels via promoting synthesis and secretion of insulin. GLP-1 and many analogues are approved for treatment of type II diabetes. Accumulating results imply that GLP-1 performs multiple functions in various tissues and organs beyond regulation of blood-glucose. The neuroprotective function of GLP-1 has been extensively explored during the past two decades. Three of our previous studies have shown that apurinic/apyrimidinic endonuclease 1 (APE1) is the only protein of the base excision repair (BER) pathway able to be regulated by oxidative stress or exogenous stimulations in rat primary cortical neurons...
August 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28842232/endoscopic-third-ventriculostomy-in-patients-with-neurofibromatosis-type-i-a-multicenter-international-experience
#7
Jonathan Roth, Roee Ber, Jeffrey H Wisoff, Eveline T Hidalgo, David D Limbrick, Daniel S Berger, Ulrich W Thomale, Matthias Schulz, Giuseppe Cinalli, Claudia Santoro, Shlomi Constantini
BACKGROUND: Hydrocephalus in patients with neurofibromatosis type I (NF1) is usually obstructive, and may arise secondary to tumoral or non-tumoral causes. The treatment of hydrocephalus in these patients is often challenging due to combined pathologies and unique anatomical changes. The use of endoscopic third ventriculostomy (ETV) as treatment has rarely been described in this group. In this study we aimed to characterize the indications, considerations and outcome of ETV in patients with NF1 gathered in a multicenter international cohort...
August 22, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28836036/modulation-of-adenylate-cyclase-signaling-in-association-with-mkk3-6-stabilization-under-combination-of-sac-and-berberine-to-reduce-hepg2-cell-survivability
#8
Dipanwita Sengupta, Kaustav Dutta Chowdhury, Sujan Chatterjee, Avik Sarkar, Soumosish Paul, Pradip Kumar Sur, Gobinda Chandra Sadhukhan
Cancer cells often have faulty apoptotic pathways resulting in sustenance of survivability, tumour metastasis and resistance to anticancer drugs. Alternate strategies are sought to improve therapeutic efficacy and therefore HepG2 cells were treated with S-allyl-cysteine (SAC) and berberine (BER) to analyze their mechanistic impact upon necroptosis along with its interacting relationship to apoptosis. In the present study we observed that SAC and BER exposure reduced NFκβ nuclear translocation through adenylate cyclase-cAMP-protein kinaseA axis and eventually evaded c-FLIP inhibition...
August 23, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28765330/genome-stability-by-dna-polymerase-%C3%AE-in-neural-progenitors-contributes-to-neuronal-differentiation-in-cortical-development
#9
Kohei Onishi, Akiko Uyeda, Mitsuhiro Shida, Teruyoshi Hirayama, Takeshi Yagi, Nobuhiko Yamamoto, Noriyuki Sugo
DNA repair is crucial for genome stability in the developing cortex, as somatic de novo mutations cause neurological disorders. However, how DNA repair contributes to neuronal development is largely unknown. To address this issue, we studied the spatiotemporal roles of DNA polymerase β (Polβ), a key enzyme in DNA base excision repair (BER) pathway, in the developing cortex using distinct forebrain-specific conditional knockout mice, Emx1-Cre/Polβ(fl/fl) and Nex-Cre/Polβ(fl/fl) mice. Polβ expression was absent in both neural progenitors and postmitotic neurons in Emx1-Cre/Polβ(fl/fl) mice, while only postmitotic neurons lacked Polβ expression in Nex-Cre/Polβ(fl/fl) mice...
August 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28761124/phaeocystis-globosa-virus-dna-polymerase-x-a-swiss-army-knife-multifunctional-dna-polymerase-lyase-ligase-for-base-excision-repair
#10
José L Fernández-García, Ana de Ory, Corina P D Brussaard, Miguel de Vega
Phaeocystis globosa virus 16T is a giant virus that belongs to the so-called nucleo-cytoplasmic large DNA virus (NCLDV) group. Its linear dsDNA genome contains an almost full complement of genes required to participate in viral base excision repair (BER). Among them is a gene coding for a bimodular protein consisting of an N-terminal Polβ-like core fused to a C-terminal domain (PgVPolX), which shows homology with NAD(+)-dependent DNA ligases. Analysis of the biochemical features of the purified enzyme revealed that PgVPolX is a multifunctional protein that could act as a "Swiss army knife" enzyme during BER since it is endowed with: 1) a template-directed DNA polymerization activity, preferentially acting on DNA structures containing gaps; 2) 5'-deoxyribose-5-phosphate (dRP) and abasic (AP) site lyase activities; and 3) an NAD(+)-dependent DNA ligase activity...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28760703/berberine-induced-cardioprotection-and-sirt3-modulation-in-doxorubicin-treated-h9c2-cardiomyoblasts
#11
Ana R Coelho, Tatiana R Martins, Renata Couto, Cláudia Deus, Cláudia V Pereira, Rui F Simões, Albert A Rizvanov, Filomena Silva, Teresa Cunha-Oliveira, Paulo J Oliveira, Teresa L Serafim
Doxorubicin (DOX) is one of the most widely used anti-neoplastic agents. However, treatment with DOX is associated with cumulative cardiotoxicity inducing progressive cardiomyocyte death. Sirtuin 3 (Sirt3), a mitochondrial deacetylase, regulates the activity of proteins involved in apoptosis, autophagy and metabolism. Our hypothesis is that pharmacological modulation by berberine (BER) pre-conditioning of Sirt3 protein levels decreases DOX-induced cardiotoxicity. Our results showed that DOX induces cell death in all experimental groups...
July 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28759018/toxicity-and-repair-of-dna-adducts-produced-by-the-natural-product-yatakemycin
#12
Elwood A Mullins, Rongxin Shi, Brandt F Eichman
Yatakemycin (YTM) is an extraordinarily toxic DNA alkylating agent with potent antimicrobial and antitumor properties and is the most recent addition to the CC-1065 and duocarmycin family of natural products. Though bulky DNA lesions the size of those produced by YTM are normally removed from the genome by the nucleotide-excision repair (NER) pathway, YTM adducts are also a substrate for the bacterial DNA glycosylases AlkD and YtkR2, unexpectedly implicating base-excision repair (BER) in their elimination. The reason for the extreme toxicity of these lesions and the molecular basis for the way they are eliminated by BER have been unclear...
September 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28752642/genome-wide-map-of-apn1-binding-sites-under-oxidative-stress-in-saccharomyces-cerevisiae
#13
Lydia P Morris, Andrew B Conley, Natalya Degtyareva, I King Jordan, Paul W Doetsch
The DNA is cells is continuously exposed to reactive oxygen species resulting in toxic and mutagenic DNA damage. Although the repair of oxidative DNA damage occurs primarily through the base excision repair (BER) pathway, the nucleotide excision repair (NER) pathway processes some of the same lesions. In addition, damage tolerance mechanisms, such as recombination and translesion synthesis, enable cells to tolerate oxidative DNA damage, especially when BER and NER capacities are exceeded. Thus, disruption of BER alone or disruption of BER and NER in Saccharomyces cerevisiae leads to increased mutations as well as large-scale genomic rearrangements...
July 27, 2017: Yeast
https://www.readbyqxmd.com/read/28749454/the-association-of-low-penetrance-variants-in-dna-repair-genes-with-colorectal-cancer-a-systematic-review-and-meta-analysis
#14
Nikhil Aggarwal, Neil D Donald, Salim Malik, Subothini S Selvendran, Mark Jw McPhail, Kevin J Monahan
OBJECTIVES: Approximately 35% of colorectal cancer (CRC) risk is attributable to heritable factors known hereditary syndromes, accounting for 6%. The remainder may be due to lower penetrance polymorphisms particularly of DNA repair genes. DNA repair pathways, including base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), direct reversal repair (DRR), and double-strand break repair are complex, evolutionarily conserved, and critical in carcinogenesis. Germline mutations in these genes are associated with high-penetrance CRC syndromes such as Lynch syndrome...
July 27, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28743242/association-between-the-xrcc1-polymorphisms-and-clinical-outcomes-of-advanced-nsclc-treated-with-platinum-based-chemotherapy-a-meta-analysis-based-on-the-prisma-statement
#15
Dan-Juan Li, Dong Xiao
BACKGROUND: Base excision repair (BER) pathway is a DNA repair pathway that is important in carcinogenesis and in response to DNA-damaging chemotherapy. XRCC1 is one of important molecular markers for BER. So far, the role of XRCC1 polymorphisms with clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy is inconclusive. To explore the relationship between XRCC1 polymorphisms and platinum-based chemotherapy in advanced NSCLC patients, we performed this meta-analysis...
July 25, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28733611/integrin-%C3%AE-6%C3%AE-4-upregulates-amphiregulin-and-epiregulin-through-base-excision-repair-mediated-dna-demethylation-and-promotes-genome-wide-dna-hypomethylation
#16
Brittany L Carpenter, Jinpeng Liu, Lei Qi, Chi Wang, Kathleen L O'Connor
Aberrant DNA methylation patterns are a common theme across all cancer types. Specific DNA demethylation of regulatory sequences can result in upregulation of genes that are critical for tumor development and progression. Integrin α6β4 is highly expressed in pancreatic carcinoma and contributes to cancer progression, in part, through the specific DNA demethylation and upregulation of epidermal growth factor receptor (EGFR) ligands amphiregulin (AREG) and epiregulin (EREG). Whole genome bisulfite sequencing (WGBS) revealed that integrin α6β4 signaling promotes an overall hypomethylated state and site specific DNA demethylation of enhancer elements within the proximal promoters of AREG and EREG...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28699540/dna-base-excision-repair-the-achilles-heel-of-tumour-cells-and-their-microenvironment
#17
M Poletto, A J Legrand, G L Dianov
Our current understanding of cancer suggests that every tumour has individual features. Approaches to cancer treatment require thorough comprehension of the mechanisms triggering genomic instability and protecting cancer cells from therapeutic treatments. Base excision repair (BER) is a frontline DNA repair system that is responsible for maintaining genome integrity. The BER pathway prevents the occurrence of disease, including cancer, by constantly repairing DNA base lesions and DNA single strand breaks caused by endogenous and exogenous mutagens...
July 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28679059/role-and-potential-targeting-of-hepatic-apurinic-apyrimidinic-endonuclease-1-and-cyclin-dependent-kinase-4-in-hepatocellular-carcinoma
#18
Kadry Sadek, Tarek Abouzed, Sherif Nasr, Moustafa Shukry
Apurinic/apyrimidinic endonuclease/redox element 1 (APE1/Ref-1) is a pervasive multifunctional protein required in the DNA base extraction repair (BER) pathway and a noteworthy reducing-oxidizing (redox) factor that upgrades the authoritative of various transcription components to DNA. Cyclin-dependent kinases (CDKs) assume a key part in directing the movement of the cell-cycle. The present study evaluates the synergistic efficacy of using licochalcone B (LCB) and fullerene C60 (FnC60) nanoparticles against diethylnitrosamine (DEN)-induced hepatocarcinoma (HCC) in rats...
July 5, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28675037/sensitive-detection-of-dna-lesions-by-bulge-enhanced-highly-specific-coamplification-at-lower-denaturation-temperature-polymerase-chain-reaction
#19
Yu Feng, Shuang Cai, Guoliang Xiong, Guanfei Zhang, Shihui Wang, Xin Su, Changyuan Yu
Mutagenic modifications of nucleotides or DNA lesions that result from environmental stress have proven to be associated with a variety of diseases, particularly cancer. The method for accurately detecting the lesions is therefore of great importance for biomedical research and toxicity study. We develop a sensitive and low-cost bulge-enhanced coamplification at lower denaturation temperature polymerase chain reaction (COLD-PCR) method for detecting DNA lesions (uracil and 8-oxoguanine) by combining an in vitro base excision repair (BER) pathway and COLD-PCR...
July 12, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28668127/kinetic-methods-for-studying-dna-glycosylases-functioning-in-base-excision-repair
#20
Christopher T Coey, Alexander C Drohat
Base excision repair (BER) is a conserved and ubiquitous pathway that is initiated by DNA glycosylases, which recognize and remove damaged or mismatched nucleobases, setting the stage for restoration of the correct DNA sequence by follow-on BER enzymes. DNA glycosylases employ a nucleotide-flipping step prior to cleavage of the N-glycosyl bond, and most exhibit slow release of the abasic DNA product and/or strong product inhibition. As such, studying the catalytic mechanism of these enzymes requires care in the design, execution, and interpretation of single- and multiple-turnover kinetics experiments, which is the topic of this chapter...
2017: Methods in Enzymology
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