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https://www.readbyqxmd.com/read/28524082/cellular-repair-of-dna-dna-cross-links-induced-by-1-2-3-4-diepoxybutane
#1
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
https://www.readbyqxmd.com/read/28515154/progerin-sequestration-of-pcna-promotes-replication-fork-collapse-and-mislocalization-of-xpa-in-laminopathy-related-progeroid-syndromes
#2
Benjamin A Hilton, Ji Liu, Brian M Cartwright, Yiyong Liu, Maya Breitman, Youjie Wang, Rowdy Jones, Hui Tang, Antonio Rusinol, Phillip R Musich, Yue Zou
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that is caused by a point mutation in the LMNA gene resulting in production of a truncated farnesylated-prelamin A protein (progerin). We previously reported that XPA mislocalized to the progerin-induced DNA double-strand break (DSB) sites, blocking DSB repair, which led to DSB accumulation, DNA damage responses, and early replication arrest in HGPS. In this study, the XPA mislocalization to DSBs occurred at stalled or collapsed replication forks, concurrent with a significant loss of PCNA at the forks, whereas PCNA efficiently bound to progerin...
May 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28509359/the-dna-translocase-rad5a-acts-independently-of-the-other-main-dna-repair-pathways-and-requires-both-its-atpase-and-ring-domain-for-activity-in-arabidopsis-thaliana
#3
Tobias Klemm, Anja Mannuß, Daniela Kobbe, Alexander Knoll, Oliver Trapp, Annika Dorn, Holger Puchta
Multiple pathways exist to repair DNA damage induced by methylating and cross-linking agents in Arabidopsis thaliana. The SWI2/SNF2 translocase RAD5A, the functional homolog of budding yeast Rad5 that is required for the error-free branch of post replicative repair, plays a surprisingly prominent role in the repair of both kinds of lesions in Arabidopsis. Here we show that both the ATPase domain and the ubiquitination function of the RING domain of the Arabidopsis protein are essential for the cellular response to different forms of DNA damage...
May 16, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28506294/hssb1-associates-with-and-promotes-stability-of-the-blm-helicase
#4
Laura V Croft, Nicholas W Ashton, Nicolas Paquet, Emma Bolderson, Kenneth J O'Byrne, Derek J Richard
BACKGROUND: Maintenance of genome stability is critical in human cells. Mutations in or loss of genome stability pathways can lead to a number of pathologies including cancer. hSSB1 is a critical DNA repair protein functioning in the repair and signalling of stalled DNA replication forks, double strand DNA breaks and oxidised DNA lesions. The BLM helicase is central to the repair of both collapsed DNA replication forks and double strand DNA breaks by homologous recombination. RESULTS: In this study, we demonstrate that hSSB1 and BLM helicase form a complex in cells and the interaction is altered in response to ionising radiation (IR)...
May 15, 2017: BMC Molecular Biology
https://www.readbyqxmd.com/read/28501701/radb-acts-in-homologous-recombination-in-the-archaeon-haloferax-volcanii-consistent-with-a-role-as-recombination-mediator
#5
Kayleigh Wardell, Sam Haldenby, Nathan Jones, Susan Liddell, Greg H P Ngo, Thorsten Allers
Homologous recombination plays a central role in the repair of double-strand DNA breaks, the restart of stalled replication forks and the generation of genetic diversity. Regulation of recombination is essential since defects can lead to genome instability and chromosomal rearrangements. Strand exchange is a key step of recombination - it is catalysed by RecA in bacteria, Rad51/Dmc1 in eukaryotes and RadA in archaea. RadB, a paralogue of RadA, is present in many archaeal species. RadB has previously been proposed to function as a recombination mediator, assisting in RadA-mediated strand exchange...
April 26, 2017: DNA Repair
https://www.readbyqxmd.com/read/28492696/complex-recombination-with-deletion-in-the-f8-and-duplication-in-the-tmlhe-mediated-by-int22h-copies-during-early-embryogenesis
#6
Changming Chen, Xiaoling Xie, Xi Wu, Yeling Lu, Xuefeng Wang, Wenman Wu, Yiqun Hu, Qiulan Ding
Haemophilia A (HA) is a common X-linked recessive bleeding disorder and almost one half of patients with severe HA are caused by intron 22 inversion (Inv22) in the F8. Inv22 is considered to be almost exclusively of meiotic origin in germ cells during spermatogenesis and only one mosaic Inv22 female carrier with the mutation possibly occurring during mitosis of the embryo has been reported so far. Previously we have identified a novel complex recombination mediated by int22h copies in a sporadic severe HA pedigree and herein we have localised the sequences flanking the breakpoint region using genome walking technique, AccuCopy technique, gene chip and real-time PCR...
May 11, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28487407/acute-inactivation-of-the-replicative-helicase-in-human-cells-triggers-mcm8-9-dependent-dna-synthesis
#7
Toyoaki Natsume, Kohei Nishimura, Sheroy Minocherhomji, Rahul Bhowmick, Ian D Hickson, Masato T Kanemaki
DNA replication fork progression can be disrupted at difficult to replicate loci in the human genome, which has the potential to challenge chromosome integrity. This replication fork disruption can lead to the dissociation of the replisome and the formation of DNA damage. To model the events stemming from replisome dissociation during DNA replication perturbation, we used a degron-based system for inducible proteolysis of a subunit of the replicative helicase. We show that MCM2-depleted cells activate a DNA damage response pathway and generate replication-associated DNA double-strand breaks (DSBs)...
May 9, 2017: Genes & Development
https://www.readbyqxmd.com/read/28482225/immunostaining-of-uva-induced-dna-damage-in-erythrocytes-of-medaka-oryzias-latipes
#8
Alaa El-Din Hamid Sayed, Hiroshi Mitani
Some authors have recently reported that UVA induces double-strand breaks (DSBs) in DNA. Only a few researchers have reported on the induction of DSBs upon UVA exposure, as measured using the Comet assay and γ-H2AX as markers of DSB formation. In the present study, we have investigated for the first time the dose-dependent induction of DSBs by UVA in medaka (Oryzias latipes) erythrocytes. Adult female medaka fish were exposed to UVA for 15, 30, and 60min/day for three continuous days; an unirradiated control group was kept in the same laboratory conditions...
April 28, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28477131/noncanonical-atm-activation-and-signaling-in-response-to-transcription-blocking-dna-damage
#9
Jurgen A Marteijn, Wim Vermeulen, Maria Tresini
Environmental genotoxins and metabolic byproducts generate DNA lesions that can cause genomic instability and disrupt tissue homeostasis. To ensure genomic integrity, cells employ mechanisms that convert signals generated by stochastic DNA damage into organized responses, including activation of repair systems, cell cycle checkpoints, and apoptotic mechanisms. DNA damage response (DDR) signaling pathways coordinate these responses and determine cellular fates in part, by transducing signals that modulate RNA metabolism...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28475600/a-new-role-for-rrm3-in-repair-of-replication-born-dna-breakage-by-sister-chromatid-recombination
#10
Sandra Muñoz-Galván, María García-Rubio, Pedro Ortega, Jose F Ruiz, Sonia Jimeno, Benjamin Pardo, Belén Gómez-González, Andrés Aguilera
Replication forks stall at different DNA obstacles such as those originated by transcription. Fork stalling can lead to DNA double-strand breaks (DSBs) that will be preferentially repaired by homologous recombination when the sister chromatid is available. The Rrm3 helicase is a replisome component that promotes replication upon fork stalling, accumulates at highly transcribed regions and prevents not only transcription-induced replication fork stalling but also transcription-associated hyper-recombination...
May 5, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28472716/combined-loss-of-three-dna-damage-response-pathways-renders-c-elegans-intolerant-to-light
#11
Ivo van Bostelen, Marcel Tijsterman
Infliction of DNA damage initiates a complex cellular reaction - the DNA damage response - that involves both signaling and DNA repair networks with many redundancies and parallel pathways. Here, we reveal the three strategies that the simple multicellular eukaryote, C. elegans, uses to deal with DNA damage induced by light. Separately inactivating repair or replicative bypass of photo-lesions results in cellular hypersensitivity towards UV-light, but impeding repair of replication associated DNA breaks does not...
April 14, 2017: DNA Repair
https://www.readbyqxmd.com/read/28467801/inhibition-of-exportin-1-function-results-in-rapid-cell-cycle-associated-dna-damage-in-cancer-cells
#12
Russell T Burke, Joshua M Marcus, James D Orth
Selective inhibitors of nuclear export (SINE) are small molecules in development as anti-cancer agents. The first-in-class SINE, selinexor, is in clinical trials for blood and solid cancers. Selinexor forms a covalent bond with exportin-1 at cysteine-528, and blocks its ability to export cargos. Previous work has shown strong cell cycle effects and drug-induced cell death across many different cancer-derived cell lines. Here, we report strong cell cycle-associated DNA double-stranded break formation upon the treatment of cancer cells with SINE...
April 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465723/a-case-with-concurrent-duplication-triplication-and-uniparental-isodisomy-at-1q42-12-qter-supporting-microhomology-mediated-break-induced-replication-model-for-replicative-rearrangements
#13
Tomohiro Kohmoto, Nana Okamoto, Takuya Naruto, Chie Murata, Yuya Ouchi, Naoko Fujita, Hidehito Inagaki, Shigeko Satomura, Nobuhiko Okamoto, Masako Saito, Kiyoshi Masuda, Hiroki Kurahashi, Issei Imoto
BACKGROUND: Complex genomic rearrangements (CGRs) consisting of interstitial triplications in conjunction with uniparental isodisomy (isoUPD) have rarely been reported in patients with multiple congenital anomalies (MCA)/intellectual disability (ID). One-ended DNA break repair coupled with microhomology-mediated break-induced replication (MMBIR) has been recently proposed as a possible mechanism giving rise to interstitial copy number gains and distal isoUPD, although only a few cases providing supportive evidence in human congenital diseases with MCA have been documented...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28453550/selective-mitochondrial-dna-degradation-following-double-strand-breaks
#14
Amandine Moretton, Frédéric Morel, Bertil Macao, Philippe Lachaume, Layal Ishak, Mathilde Lefebvre, Isabelle Garreau-Balandier, Patrick Vernet, Maria Falkenberg, Géraldine Farge
Mitochondrial DNA (mtDNA) can undergo double-strand breaks (DSBs), caused by defective replication, or by various endogenous or exogenous sources, such as reactive oxygen species, chemotherapeutic agents or ionizing radiations. MtDNA encodes for proteins involved in ATP production, and maintenance of genome integrity following DSBs is thus of crucial importance. However, the mechanisms involved in mtDNA maintenance after DSBs remain unknown. In this study, we investigated the consequences of the production of mtDNA DSBs using a human inducible cell system expressing the restriction enzyme PstI targeted to mitochondria...
2017: PloS One
https://www.readbyqxmd.com/read/28453412/identification-and-characterization-of-citrus-tristeza-virus-isolates-breaking-resistance-in-trifoliate-orange-in-california
#15
Raymond K Yokomi, Vijayanandraj Selvaraj, Yogita Maheshwari, Maria Saponari, Annalisa Giampetruzzi, Michela Chiumenti, Subhas Hajeri
Most Citrus tristeza virus (CTV) isolates in California are biologically mild and symptomless in commercial cultivars on CTV tolerant rootstocks. However, to better define California CTV isolates showing divergent serological and genetic profiles, selected isolates were subjected to deep sequencing of small RNAs. Full-length sequences were assembled, annotated and trifoliate orange resistance-breaking (RB) isolates of CTV were identified. Phylogenetic relationships based on their full genomes placed three isolates in the RB clade: CA-RB-115, CA-RB-AT25, and CA-RB-AT35...
April 28, 2017: Phytopathology
https://www.readbyqxmd.com/read/28448050/single-molecule-analysis-of-laser-localized-psoralen-adducts
#16
Jing Huang, Himabindu Gali, Julia Gichimu, Marina A Bellani, Durga Pokharel, Manikandan Paramasivam, Michael M Seidman
The DNA Damage Response (DDR) has been extensively characterized in studies of double strand breaks (DSBs) induced by laser micro beam irradiation in live cells. The DDR to helix distorting covalent DNA modifications, including interstrand DNA crosslinks (ICLs), is not as well defined. We have studied the DDR stimulated by ICLs, localized by laser photoactivation of immunotagged psoralens, in the nuclei of live cells. In order to address fundamental questions about adduct distribution and replication fork encounters, we combined laser localization with two other technologies...
April 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28436335/localization-of-the-werner-protein-together-with-h2ax-in-%C3%AE-irradiation-induced-neoplastic-transformed-human-mesenchymal-stem-cells
#17
Nedime Serakinci, Tufan Cankaya, Steen Kølvraa
The H2A histone family, member X (H2AX), and Werner (WRN) are important proteins for genome and telomere maintenance. WRN has a major role in genome stability, particularly during DNA replication, transcription, recombination, and repair of DNA double-stranded breaks (DSBs) via base excision repair, homologous recombination, or nonhomologous end joining. H2AX plays a part in the rapid, sensitive, cellular response to the ionizing radiation or DNA-damaging chemotherapeutic agents that cause DSBs. This occurs when radiation-induced DSBs trigger the activation of H2AX and begin the damage-repair process...
2017: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/28427283/break-induced-replication-in-eukaryotes-mechanisms-functions-and-consequences
#18
Cynthia J Sakofsky, Anna Malkova
Break-induced replication (BIR) is an important pathway specializing in repair of one-ended double-strand DNA breaks (DSBs). This type of DSB break typically arises at collapsed replication forks or at eroded telomeres. BIR initiates by invasion of a broken DNA end into a homologous template followed by initiation of DNA synthesis that can proceed for hundreds of kilobases. This synthesis is drastically different from S-phase replication in that instead of a replication fork, BIR proceeds via a migrating bubble and is associated with conservative inheritance of newly synthesized DNA...
April 21, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28418813/radiation-induced-deletions-in-mouse-spermatogonia-are-usually-large-over-200-kb-and-contain-little-sequence-similarity-at-the-junctions
#19
Mieko Kodaira, Jun-Ichi Asakawa, Nori Nakamura
Ionizing radiation can induce mutations, and the majority of radiation-induced mutations in mammalian cells are deletions. The most critical types of radiation-induced DNA damage are DNA double-strand breaks, and these breaks are repaired by either the homologous recombination (HR) pathway or the non-homologous end joining (NHEJ) pathway. The HR pathway is not as mutagenic as the NHEJ pathway, and it is expected that radiation-induced deletions would usually have little sequence similarity around the deletion junction points...
April 18, 2017: Radiation Research
https://www.readbyqxmd.com/read/28416484/ssrp1-cooperates-with-parp-and-xrcc1-to-facilitate-single-strand-dna-break-repair-by-chromatin-priming
#20
Ying Gao, Changling Li, Leizhen Wei, Yaqun Teng, Satoshi Nakajima, Xiukai Chen, Jianquan Xu, Brittany Leger, Hongqiang Ma, Stephen Spagnol, Yong Wan, Kris Dahl, Yang Liu, Arthur Levine, Li Lan
DNA single strand breaks (SSB) are the most common form of DNA damage, requiring repair processes that to initiate must overcome chromatin barriers. The FACT complex comprised of the SSRP1 and SPT16 proteins are important for maintaining chromatin integrity, with SSRP1 acting as an histone H2A/H2B chaperone in chromatin disassembly during DNA transcription, replication and repair. In this study, we show that SSRP1 but not SPT16 is critical for cell survival after ionizing radiation or methyl methanesulfonate-induced single-strand DNA damage...
April 17, 2017: Cancer Research
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