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https://www.readbyqxmd.com/read/28634400/chronic-treatment-with-cisplatin-induces-chemoresistance-through-the-tip60-mediated-fanconi-anemia-and-homologous-recombination-repair-pathways
#1
Wen-Pin Su, Yen-Chih Ho, Cheng-Kuei Wu, Sen-Huei Hsu, Jia-Lin Shiu, Jheng-Cheng Huang, Song-Bin Chang, Wen-Tai Chiu, Jan-Jong Hung, Tsung-Lin Liu, Wei-Sheng Wu, Pei-Yu Wu, Wu-Chou Su, Jang-Yang Chang, Hungjiun Liaw
The Fanconi anemia pathway in coordination with homologous recombination is essential to repair interstrand crosslinks (ICLs) caused by cisplatin. TIP60 belongs to the MYST family of acetyltransferases and is involved in DNA repair and regulation of gene transcription. Although the physical interaction between the TIP60 and FANCD2 proteins has been identified that is critical for ICL repair, it is still elusive whether TIP60 regulates the expression of FA and HR genes. In this study, we found that the chemoresistant nasopharyngeal carcinoma cells, derived from chronic treatment of cisplatin, show elevated expression of TIP60...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28627616/distinct-cellular-phenotype-linked-to-defective-dna-interstrand-crosslink-repair-and-homologous-recombination
#2
Aleksandra M Gorniewska, Katarzyna Kluzek, Lidia Gackowska, Izabela Kubiszewska, Malgorzata Z Zdzienicka, Aneta Bialkowska
Repair of DNA interstrand crosslinks (ICLs) predominantly involves the Fanconi anemia (FA) pathway and homologous recombination (HR). The HR repair system eliminates DNA double strand breaks (DSBs) that emerge during ICLs removal. The current study presents a novel cell line, CL‑V8B, representing a new complementation group of Chinese hamster cell mutants hypersensitive to DNA crosslinking factors. CL‑V8B exhibits increased sensitivity to various DNA‑damaging agents, including compounds leading to DSBs formation (bleomycin and 6‑thioguanine), and is extremely sensitive to poly (ADP-ribose) polymerase inhibitor (>400‑fold), which is typical for HR‑defective cells...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627569/porphyrin-based-photosensitizers-and-their-dna-conjugates-for-singlet-oxygen-induced-nucleic-acid-interstrand-crosslinking
#3
Eva M Llamas, João P C Tome, João M M Rodrigues, Tomás Torres, Annemieke Madder
The development of methods for the generation of site-selective interstrand crosslinks (ICLs) in synthetic oligonucleotides provides a platform for the study of ICL repair mechanisms and the stabilisation of DNA-based materials. Our group has previously reported on the use of a furan moiety as a masked reactive functionality for ICL generation and recently introduced the use of (1)O2 as an efficient light-induced oxidant. Here, the use of porphyrin-based photosensitizers (PSs) has been explored for ICL generation...
June 19, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28623094/structural-and-functional-relationships-of-fan1
#4
REVIEW
Hyeonseok Jin, Yunje Cho
FANCD2/FANCI-associated nuclease (FAN1) is a 5' flap structure-specific endonuclease and 5' to 3' exonuclease. This nuclease can resolve interstrand cross-links (ICLs) independently of the Fanconi anemia (FA) pathway and controls the progression of stalled replication forks in an FA-dependent manner, thereby maintaining chromosomal stability. Several FAN1 mutations are observed in various cancers and degenerative diseases. Recently, several crystal structures of the FAN1-DNA complexes have been reported, and to date, these represent the only structures for a DNA bound ICL-repair nuclease...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28621132/one-pot-consecutive-sulfonamidation-ipso-cyclization-strategy-for-the-construction-of-azaspirocyclohexadienones
#5
Chada Raji Reddy, Ravi Ranjan, Santosh Kumar Prajapati, Kamalkishor Warudikar
Harnessing of Morita-Baylis-Hillman (MBH) carbonates of acetylenic aldehydes as handy synthons has allowed a facile synthesis of azaspirocyclohexadienones by sequential DABCO-promoted sulfonamidation/ICl-mediated ipso-iodocyclization reactions. A variety of MBH-carbonates having aryl or heteroaryl groups on the alkyne functionality fruitfully participated in the one-pot ipso-annulation reaction to provide the corresponding 3-iodo spirocyclohexadienones. The sulphonamide funtionality was further utilized to construct the tricyclic fused-sultam framework...
June 16, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28611132/posterior-chamber-phakic-intraocular-lens-implantation-comparative-multicentre-study-in-351-eyes-with-low-to-moderate-or-high-myopia
#6
Kazutaka Kamiya, Kimiya Shimizu, Akihito Igarashi, Yoshihiro Kitazawa, Takashi Kojima, Tomoaki Nakamura, Yoshitaka Oka, Rei Matsumoto
AIM: To compare the clinical outcomes of posterior chamber phakic intraocular lens implantation with a central hole (Hole Implantable Collamer Lens (ICL), STAAR Surgical) for low-to-moderate myopia and for high myopia. METHODS: This multicentre retrospective case series comprised 351 eyes of 351 consecutive patients undergoing ICL implantation. Eyes were divided into groups based on preoperative degree of myopia: group 1; 57 eyes, manifest spherical equivalent less than -6 dioptres (D), and group 2; 294 eyes, -6 D or more...
June 13, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28607004/rpa-activates-the-xpf-ercc1-endonuclease-to-initiate-processing-of-dna-interstrand-crosslinks
#7
Ummi B Abdullah, Joanna F McGouran, Sanja Brolih, Denis Ptchelkine, Afaf H El-Sagheer, Tom Brown, Peter J McHugh
During replication-coupled DNA interstrand crosslink (ICL) repair, the XPF-ERCC1 endonuclease is required for the incisions that release, or "unhook", ICLs, but the mechanism of ICL unhooking remains largely unknown. Incisions are triggered when the nascent leading strand of a replication fork strikes the ICL Here, we report that while purified XPF-ERCC1 incises simple ICL-containing model replication fork structures, the presence of a nascent leading strand, modelling the effects of replication arrest, inhibits this activity...
June 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28603639/folding-correction-of-abc-transporter-abcb1-by-pharmacological-chaperones-a-mechanistic-concept
#8
Matthias Spork, Muhammad Imran Sohail, Diethart Schmid, Gerhard F Ecker, Michael Freissmuth, Peter Chiba, Thomas Stockner
Point mutations of ATP-binding cassette (ABC) proteins are a common cause of human diseases. Available crystal structures indicate a similarity in the architecture of several members of this protein family. Their molecular architecture makes these proteins vulnerable to mutation, when critical structural elements are affected. The latter preferentially involve the two transmembrane domain (TMD)/nucleotide-binding domain (NBD) interfaces (transmission interfaces), formation of which requires engagement of coupling helices of intracellular loops with NBDs...
June 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28595394/surprising-behaviors-in-the-temperature-dependent-kinetics-of-diatomic-interhalogens-with-anions-and-cations
#9
Nicholas S Shuman, Oscar Martinez, Shaun G Ard, Justin P Wiens, Nicholas R Keyes, Hua Guo, Albert A Viggiano
Rate constants and product branching fractions of reactions between diatomic interhalogens (ICl, ClF) and a series of anions (Br(-), I(-)) and cations (Ar(+), N2(+)) are measured using a selected ion flow tube apparatus and reported over the temperature range 200-500 K. The efficiency of both anion reactions with ICl is 2%-3% at 300 K to yield Cl(-), increasing with temperature in a manner consistent with the small endothermicities of the reactions. The anion reactions with ClF are 10%-20% efficient at 300 K to yield Cl(-) and also show a positive temperature dependence despite being highly exothermic...
June 7, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28586500/implantation-of-implantable-collamer-lenses-after-radial-keratotomy
#10
Bárbara Martín-Escuer, José F Alfonso, José J Esteve-Taboada, Luis Fernández-Vega Cueto, Robert Montés-Micó
PURPOSE: To assess the predictability, efficacy, and safety of posterior chamber phakic implantable collamer lens (ICL) implantation after radial keratotomy. METHODS: In a retrospective non-comparative interventional case series, outcomes in 6 consecutive eyes of 4 patients with residual refraction after radial keratotomy were analyzed after the implantation of ICLs. All of the lenses were implanted to correct the residual refractive error, ranging from -12.00 to +3...
June 1, 2017: Journal of Refractive Surgery
https://www.readbyqxmd.com/read/28575657/rpa-mediated-recruitment-of-the-e3-ligase-rfwd3-is-vital-for-interstrand-crosslink-repair-and-human-health
#11
Laura Feeney, Ivan M Muñoz, Christophe Lachaud, Rachel Toth, Paul L Appleton, Detlev Schindler, John Rouse
Defects in the repair of DNA interstrand crosslinks (ICLs) are associated with the genome instability syndrome Fanconi anemia (FA). Here we report that cells with mutations in RFWD3, an E3 ubiquitin ligase that interacts with and ubiquitylates replication protein A (RPA), show profound defects in ICL repair. An amino acid substitution in the WD40 repeats of RFWD3 (I639K) found in a new FA subtype abolishes interaction of RFWD3 with RPA, thereby preventing RFWD3 recruitment to sites of ICL-induced replication fork stalling...
June 1, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28573107/rega-plays-a-key-role-in-oxygen-dependent-establishment-of-persistence-and-in-isocitrate-lyase-activity-a-critical-determinant-of-in-vivo-brucella-suis-pathogenicity
#12
Elias Abdou, María P Jiménez de Bagüés, Ignacio Martínez-Abadía, Safia Ouahrani-Bettache, Véronique Pantesco, Alessandra Occhialini, Sascha Al Dahouk, Stephan Köhler, Véronique Jubier-Maurin
For aerobic human pathogens, adaptation to hypoxia is a critical factor for the establishment of persistent infections, as oxygen availability is low inside the host. The two-component system RegB/A of Brucella suis plays a central role in the control of respiratory systems adapted to oxygen deficiency, and in persistence in vivo. Using an original "in vitro model of persistence" consisting in gradual oxygen depletion, we compared transcriptomes and proteomes of wild-type and ΔregA strains to identify the RegA-regulon potentially involved in the set-up of persistence...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28552166/activation-of-the-fa-pathway-mediated-by-phosphorylation-and-ubiquitination
#13
REVIEW
Masamichi Ishiai, Koichi Sato, Junya Tomida, Hiroyuki Kitao, Hitoshi Kurumizaka, Minoru Takata
Fanconi anemia (FA) is a devastating hereditary condition that impacts genome integrity, leading to clinical features such as skeletal and visceral organ malformations, attrition of bone marrow stem cells, and carcinogenesis. At least 21 proteins, when absent or defective, have been implicated in this disorder, and they together constitute the FA pathway, which functions in detection and repair of, and tolerance to, endogenous DNA damage. The damage primarily handled by the FA pathway has been assumed to be related to DNA interstrand crosslinks (ICLs)...
May 5, 2017: Mutation Research
https://www.readbyqxmd.com/read/28549257/human-somatic-cells-deficient-for-rad52-are-impaired-for-viral-integration-and-compromised-for-most-aspects-of-homology-directed-repair
#14
Yinan Kan, Nizar N Batada, Eric A Hendrickson
Homology-directed repair (HDR) maintains genomic integrity by eliminating lesions such as DNA double-strand breaks (DSBs), interstrand crosslinks (ICLs) and stalled replication forks and thus a deficiency in HDR is associated with genomic instability and cancer predisposition. The mechanism of HDR is best understood and most rigorously characterized in yeast. The inactivation of the fungal radiation sensitive 52 (RAD52) gene, which has both recombination mediator and single-strand annealing (SSA) activities in vitro, leads to severe HDR defects in vivo...
May 10, 2017: DNA Repair
https://www.readbyqxmd.com/read/28542210/drosophila-dna-polymerase-theta-utilizes-both-helicase-like-and-polymerase-domains-during-microhomology-mediated-end-joining-and-interstrand-crosslink-repair
#15
Kelly Beagan, Robin L Armstrong, Alice Witsell, Upasana Roy, Nikolai Renedo, Amy E Baker, Orlando D Schärer, Mitch McVey
Double strand breaks (DSBs) and interstrand crosslinks (ICLs) are toxic DNA lesions that can be repaired through multiple pathways, some of which involve shared proteins. One of these proteins, DNA Polymerase θ (Pol θ), coordinates a mutagenic DSB repair pathway named microhomology-mediated end joining (MMEJ) and is also a critical component for bypass or repair of ICLs in several organisms. Pol θ contains both polymerase and helicase-like domains that are tethered by an unstructured central region. While the role of the polymerase domain in promoting MMEJ has been studied extensively both in vitro and in vivo, a function for the helicase-like domain, which possesses DNA-dependent ATPase activity, remains unclear...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28535560/nomogram-for-predicting-intradiscal-cement-leakage-following-percutaneous-vertebroplasty-in-patients-with-osteoporotic-related-vertebral-compression-fractures
#16
Bin-Yan Zhong, Shi-Cheng He, Hai-Dong Zhu, Tao Pan, Wen Fang, Li Chen, Jin-He Guo, Gang Deng, Guang-Yu Zhu, Gao-Jun Teng
BACKGROUND: Intradiscal cement leakage (ICL) is a common complication following percutaneous vertebroplasty (PVP). However, the risk factors for such a complication are under debate and there is no accurate predictive nomogram to predict ICL. OBJECTIVES: To establish an effective and novel nomogram for ICL following PVP in patients with osteoporotic-related vertebral compression fractures (OVCFs). STUDY DESIGN: This was a retrospective study approved by the Institutional Review Board of our institution...
May 2017: Pain Physician
https://www.readbyqxmd.com/read/28535027/arsenite-binds-to-the-ring-finger-domain-of-fancl-e3-ubiquitin-ligase-and-inhibits-dna-interstrand-crosslink-repair
#17
Ji Jiang, Marina Bellani, Lin Li, Pengcheng Wang, Michael M Seidman, Yinsheng Wang
Human exposure to arsenic in drinking water is known to be associated with the development of bladder, lung, kidney, and skin cancers. The molecular mechanisms underlying the carcinogenic effects of arsenic species remain incompletely understood. DNA interstrand cross-links (ICLs) are among the most cytotoxic type of DNA lesions that block DNA replication and transcription, and these lesions can be induced by endogenous metabolism and by exposure to exogenous agents. Fanconi anemia (FA) is a congenital disorder manifested with elevated sensitivity toward DNA interstrand cross-linking agents, and monoubiquitination of FANCD2 by FANCL is a crucial step in FA-mediated DNA repair...
June 1, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28530598/understanding-the-fine-structure-of-intermediate-materials-of-maize-starches
#18
Wenfang Han, Binjia Zhang, Jiangtao Li, Siming Zhao, Meng Niu, Caihua Jia, Shanbai Xiong
Here we concern the molecular fine structure of intermediate material (IM) fraction in regular maize starch (RMS) and Starpro 40 maize starch (S40). IM had a branching degree and a molar mass (Mw) somewhere between amylopectin (AP) and amylose (AM). Compared with AP, IM had more extra-long (Fr I) and long (Fr II) chains and fb3-chains (degree of polymerization (DP)>36), with a higher average chain length (CL). Also, IM contained less A-chains but more B-chains (both BS-chains with DP 3-25 and BL-chains with DP≥26), accompanied by longer B- and BL-chains, total internal chains (TICL) and average internal chains (ICL), and a similar average external chain length (ECL)...
October 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28524769/machine-learning-for-epigenetics-and-future-medical-applications
#19
Lawrence B Holder, M Muksitul Haque, Michael K Skinner
Understanding epigenetic processes holds immense promise for medical applications. Advances in Machine Learning (ML) are critical to realize this promise. Previous studies used epigenetic data sets associated with the germline transmission of epigenetic transgenerational inheritance of disease and novel ML approaches to predict genome-wide locations of critical epimutations. A combination of Active Learning (ACL) and Imbalanced Class Learning (ICL) was used to address past problems with ML to develop a more efficient feature selection process and address the imbalance problem in all genomic data sets...
May 19, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28524082/cellular-repair-of-dna-dna-cross-links-induced-by-1-2-3-4-diepoxybutane
#20
Lisa N Chesner, Amanda Degner, Dewakar Sangaraju, Shira Yomtoubian, Susith Wickramaratne, Bhaskar Malayappan, Natalia Tretyakova, Colin Campbell
Xenobiotic-induced interstrand DNA-DNA cross-links (ICL) interfere with transcription and replication and can be converted to toxic DNA double strand breaks. In this work, we investigated cellular responses to 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD) cross-links induced by 1,2,3,4-diepoxybutane (DEB). High pressure liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI⁺-MS/MS) assays were used to quantify the formation and repair of bis-N7G-BD cross-links in wild-type Chinese hamster lung fibroblasts (V79) and the corresponding isogenic clones V-H1 and V-H4, deficient in the XPD and FANCA genes, respectively...
May 18, 2017: International Journal of Molecular Sciences
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