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https://www.readbyqxmd.com/read/28528322/very-low-doses-of-heavy-oxygen-ion-radiation-induce-premature-ovarian-failure
#1
Birendra Mishra, Ryan Ripperdan, Laura Ortiz, Ulrike Luderer
Astronauts are exposed to charged particles during space travel, and charged particles are also used for cancer radiotherapy. Premature ovarian failure is a well-known side-effect of conventional, low linear energy transfer (LET) cancer radiotherapy, but little is known about the effects of high LET charged particles on the ovary. We hypothesized that lower LET (16.5 keV/µm) oxygen particles would be less damaging to the ovary than we previously found for iron (LET=179 keV/µm). Adult female mice were irradiated with 0, 5, 30, or 50 cGy oxygen ions or 50 cGy oxygen plus dietary supplementation with the antioxidant alpha lipoic acid (ALA)...
May 20, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28527786/sumo-in-the-dna-double-stranded-break-response-similarities-differences-and-co-operation-with-ubiquitin
#2
REVIEW
Joanna R Morris, Alexander J Garvin
In recent years our knowledge of the varied role that ubiquitination plays in promoting signal amplification, novel protein interactions and protein turn-over has progressed rapidly. This is particularly remarkable in the examination of how DNA Double-Strand Breaks (DSBs) are repaired, with many components of the ubiquitin conjugation, de-conjugation and recognition machinery now identified as key factors in DSB repair. In addition, a member of the ubiquitin-like family, SUMO (Small Ubiquitin-like Modifier) has also been recognised as integral for efficient repair...
May 17, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28527403/interplay-between-bacillus-subtilis-recd2-and-the-recg-or-ruvab-helicase-in-recombinational-repair
#3
Rubén Torres, Hector Romero, Violeta Rodríguez-Cerrato, Juan C Alonso
Bacillus subtilis AddAB, RecS, RecQ, PcrA, HelD, DinG, RecG, RuvAB, PriA and RecD2 are genuine recombinational repair enzymes, but the biological role of RecD2 is poorly defined. A ΔrecD2 mutation sensitizes cells to DNA-damaging agents that stall or collapse replication forks. We found that this ΔrecD2 mutation impaired growth, and that a mutation in the pcrA gene (pcrA596) relieved this phenotype. The ΔrecD2 mutation was not epistatic to ΔaddAB, ΔrecQ, ΔrecS, ΔhelD, pcrA596 and ΔdinG, but epistatic to recA...
May 12, 2017: DNA Repair
https://www.readbyqxmd.com/read/28527011/the-prdm9-krab-domain-is-required-for-meiosis-and-involved-in-protein-interactions
#4
Yukiko Imai, Frédéric Baudat, Miguel Taillepierre, Marcello Stanzione, Attila Toth, Bernard de Massy
PR domain-containing protein 9 (PRDM9) is a major regulator of the localization of meiotic recombination hotspots in the human and mouse genomes. This role involves its DNA-binding domain, which is composed of a tandem array of zinc fingers, and PRDM9-dependent trimethylation of histone H3 at lysine 4. PRDM9 is a member of the PRDM family of transcription regulators, but unlike other family members, it contains a Krüppel-associated box (KRAB)-related domain that is predicted to be a potential protein interaction domain...
May 19, 2017: Chromosoma
https://www.readbyqxmd.com/read/28526807/dihydroartemisinin-induces-autophagy-dependent-death-in-human-tongue-squamous-cell-carcinoma-cells-through-dna-double-strand-break-mediated-oxidative-stress
#5
Xinli Shi, Li Wang, Xiaoming Li, Jing Bai, Jianchun Li, Shenghao Li, Zeming Wang, Mingrui Zhou
Dihydroartemisinin is an effective antimalarial agent with multiple biological activities. In the present investigation, we elucidated its therapeutic potential and working mechanism on human tongue squamous cell carcinoma (TSCC). It was demonstrated that dihydroartemisinin could significantly inhibit cell growth in a dose- and time-dependent manner by the Cell Counting Kit-8 and colony formation assay in vitro. Meanwhile, autophagy was promoted in the Cal-27 cells treated by dihydroartemisinin, evidenced by increased LC3B-II level, increased autophagosome formation, and increased Beclin-1 level compared to dihydroartemisinin-untreated cells...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28526682/aeroallergens-induce-reactive-oxygen-species-production-and-dna-damage-and-dampen-antioxidant-responses-in-bronchial-epithelial-cells
#6
Tze Khee Chan, W S Daniel Tan, Hong Yong Peh, W S Fred Wong
Exposure to environmental allergens is a major risk factor for asthma development. Allergens possess proteolytic activity that is capable of disrupting the airway epithelium. Although there is increasing evidence pointing to asthma as an epithelial disease, the underlying mechanism that drives asthma has not been fully elucidated. In this study, we investigated the direct DNA damage potential of aeroallergens on human bronchial epithelial cells and elucidated the mechanisms mediating the damage. Human bronchial epithelial cells, BEAS-2B, directly exposed to house dust mites (HDM) resulted in enhanced DNA damage, as measured by the CometChip and the staining of DNA double-strand break marker, γH2AX...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28526069/xlf-mediated-nhej-activity-in-hepatocellular-carcinoma-therapy-resistance
#7
Sitian Yang, Xiao Qi Wang
BACKGROUND: DNA repair pathways are used by cancer cells to overcome many standard anticancer treatments, causing therapy resistance. Here, we investigated the role of XRCC4-like factor (XLF), a core member of the non-homologous end joining (NHEJ) repair pathway, in chemoresistance in hepatocellular carcinoma (HCC). METHODS: qRT-PCR analysis and western blotting were performed to detect expression levels of genes and proteins related to NHEJ. NHEJ repair capacity was assessed in vitro (cell-free) and in vivo by monitoring the activity of the NHEJ pathway...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28525744/ctf4-prevents-genome-rearrangements-by-suppressing-dna-double-strand-break-formation-and-its-end-resection-at-arrested-replication-forks
#8
Mariko Sasaki, Takehiko Kobayashi
Arrested replication forks lead to DNA double-strand breaks (DSBs), which are a major source of genome rearrangements. Yet DSB repair in the context of broken forks remains poorly understood. Here we demonstrate that DSBs that are formed at arrested forks in the budding yeast ribosomal RNA gene (rDNA) locus are normally repaired by pathways dependent on the Mre11-Rad50-Xrs2 complex but independent of HR. HR is also dispensable for DSB repair at stalled forks at tRNA genes. In contrast, in cells lacking the core replisome component Ctf4, DSBs are formed more frequently, and these DSBs undergo end resection and HR-mediated repair that is prone to rDNA hyper-amplification; this highlights Ctf4 as a key regulator of DSB end resection at arrested forks...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28525650/detection-of-damage-on-single-or-double-stranded-dna-in-a-population-exposed-to-arsenic-in-drinking-water
#9
J Jiménez-Villarreal, D I Rivas-Armendariz, C P Pineda-Belmontes, N D Betancourt-Martínez, M A Macías-Corral, A J Guerra-Alanis, M S Niño-Castañeda, J Morán-Martínez
Different studies have suggested an association between arsenic (As) exposure and damage to single-stranded DNA by reactive oxygen species derived from the biotransformation of arsenic. The single strand damages are converted to double strand damage upon interaction with ultraviolet radiation. Analysis of genomic integrity is important for assessing the genotoxicity caused by environmental pollutants. In this study, we compared the concentration of As in drinking water, nutritional status, lifestyle variables, and the level of genotoxicity in an exposed population and a control group...
May 18, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28524082/cellular-repair-of-dna-dna-cross-links-induced-by-1-2-3-4-diepoxybutane
#10
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/28522541/a-novel-histone-crosstalk-pathway-important-for-regulation-of-uv-induced-dna-damage-repair-in-saccharomyces-cerevisiae
#11
Anna L Boudoures, Jacob J Pfeil, Elizabeth M Steenkiste, Rachel A Hoffman, Elizabeth A Bailey, Sara E Wilkes, Sarah K Higdon, Jeffrey S Thompson
Histone post-translational modifications play vital roles in a variety of nuclear processes, including DNA repair. It has been previously shown that histone H3K79 methylation is important for the cellular response to DNA damage caused by ultraviolet (UV) radiation, with evidence that specific methylation states play distinct roles in UV repair. Here we report that H3K79 methylation is reduced in response to UV exposure in Saccharomyces cerevisiae This reduction is specific to the dimethylated state, as trimethylation levels are minimally altered by UV exposure...
May 18, 2017: Genetics
https://www.readbyqxmd.com/read/28522325/generation-of-chromosomal-translocations-that-lead-to-conditional-fusion-protein-expression-using-crispr-cas9-and-homology-directed-repair
#12
Fabio Vanoli, Maria Jasin
Recurrent chromosomal translocations often lead to expression of fusion proteins associated with oncogenic transformation. To study translocations and downstream events, genome editing techniques have been developed to generate chromosomal translocations through non-homologous end joining of DNA double-strand breaks introduced at the two participating endogenous loci. However, the frequencies at which these events occur is usually too low to efficiently clone cells carrying the translocation. This article provides a detailed method using CRISPR-Cas9 technology and homology-directed repair to efficiently isolate cells harboring a chromosomal translocation...
May 15, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28521962/the-functional-roles-of-pml-nuclear-bodies-in-genome-maintenance
#13
REVIEW
Hae Ryung Chang, Anudari Munkhjargal, Myung-Jin Kim, Seon Young Park, Eunyoung Jung, Jae-Ha Ryu, Young Yang, Jong-Seok Lim, Yonghwan Kim
In the nucleus, there are several membraneless structures called nuclear bodies. Among them, promyelocytic leukemia nuclear bodies (PML-NBs) are involved in multiple genome maintenance pathways including the DNA damage response, DNA repair, telomere homeostasis, and p53-associated apoptosis. In response to DNA damage, PML-NBs are coalesced and divided by a fission mechanism, thus increasing their number. PML-NBs also play a role in repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). Clinically, the dominant negative PML-RARα fusion protein expressed in acute promyelocytic leukemia (APL) inhibits the transactivation of downstream factors and disrupts PML function, revealing the tumor suppressor role of PML-NBs...
May 5, 2017: Mutation Research
https://www.readbyqxmd.com/read/28521290/mir-2964a-5p-binding-site-snp-regulates-atm-expression-contributing-to-age-related-cataract-risk
#14
Han Rong, Shanshan Gu, Guowei Zhang, Lihua Kang, Mei Yang, Junfang Zhang, Xinyue Shen, Huaijin Guan
This study was to explore the involvement of DNA repair genes in the pathogenesis of age-related cataract (ARC). We genotyped nine single nucleotide polymorphisms (SNPs) of genes responsible to DNA double strand breaks (DSBs) in 804 ARC cases and 804 controls in a cohort of eye diseases in Chinese population and found that the ataxia telangiectasia mutated (ATM) gene-rs4585:G>T was significantly associated with ARC risk. An in vitro functional test found that miR-2964a-5p specifically down-regulated luciferase reporter expression and ATM expression in the cell lines transfected with rs4585 T allele compared to rs4585 G allele...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515316/dna-damage-induced-degradation-of-exo1-limits-dna-end-resection-to-ensure-accurate-dna-repair
#15
Nozomi Tomimatsu, Bipasha Mukherjee, Janelle Louise Harris, Francesca Ludovica Boffo, Molly Hardebeck, Patrick Ryan Potts, Kum Kum Khanna, Sandeep Burma
End resection of DNA double-strand breaks (DSBs) to generate 3'-single-stranded DNA facilitates DSB repair via error-free homologous recombination (HR) while stymieing repair by the error-prone non-homologous end joining (NHEJ) pathway. Activation of DNA end resection involves phosphorylation of the 5' to 3' exonuclease EXO1 by the phosphoinositide 3-kinase-like kinases ATM and ATR, and by the cyclin-dependent kinases 1 and 2. After activation, EXO1 must also be restrained in order to prevent over-resection which is known to hamper optimal HR and trigger global genomic instability...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515154/progerin-sequestration-of-pcna-promotes-replication-fork-collapse-and-mislocalization-of-xpa-in-laminopathy-related-progeroid-syndromes
#16
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/28514723/genomic-profiling-of-pelvic-genital-type-leiomyosarcoma-in-a-woman-with-a-germline-chek2-c-1100delc-mutation-and-a-concomitant-diagnosis-of-metastatic-invasive-ductal-breast-carcinoma
#17
My Linh Thibodeau, Caralyn Reisle, Eric Zhao, Lee Ann Martin, Yazeed Alwelaie, Karen L Mungall, Carolyn Ch'ng, Ruth Thomas, Tony Ng, Stephen Yip, Howard Lim, Sophie Sun, Sean S Young, Aly Karsan, Yongjun Zhao, Andrew J Mungall, Richard A Moore, Daniel Renouf, Karen Gelmon, Yussanne P Ma, Malcolm Hayes, Janessa Laskin, Marco A Marra, Kasmintan A Schrader, Steven J M Jones
INTRODUCTION: We describe a woman with the known pathogenic germline variant CHEK2:c.1100delC and synchronous diagnoses of both pelvic genital type leiomyosarcoma and metastatic invasive ductal breast carcinoma. CHEK2 (checkpoint kinase 2) is a tumour suppressor gene encoding a serine/threonine-protein kinase (CHEK2) involved in double-strand DNA break repair and cell cycle arrest. The CHEK2:c.1100delC variant is a moderate penetrance allele resulting in an approximate 2-fold increase in breast cancer risk...
May 16, 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28514650/the-ino80-complex-removes-h2a-z-to-promote-presynaptic-filament-formation-during-homologous-recombination
#18
Claudio A Lademann, Jörg Renkawitz, Boris Pfander, Stefan Jentsch
The INO80 complex (INO80-C) is an evolutionarily conserved nucleosome remodeler that acts in transcription, replication, and genome stability. It is required for resistance against genotoxic agents and is involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). However, the causes of the HR defect in INO80-C mutant cells are controversial. Here, we unite previous findings using a system to study HR with high spatial resolution in budding yeast. We find that INO80-C has at least two distinct functions during HR-DNA end resection and presynaptic filament formation...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28514062/locoregional-therapy-with-%C3%AE-emitting-trastuzumab-against-peritoneal-metastasis-of-her2-positive-gastric-cancer-in-mice
#19
Huizi Keiko Li, Yukie Morokoshi, Kotaro Nagatsu, Tadashi Kamada, Sumitaka Hasegawa
Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found however that locoregionally administered trastuzumab armed with a radionuclide astatine-211 ((211) At)-emitting α-particle ((211) At-trastuzumab) is effective against HER2-positive PMGC in a xenograft mouse model. We first observed that (211) At-trastuzumab can specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2-positive human metastatic GC cells, both in vitro and in subcutaneous tumors...
May 17, 2017: Cancer Science
https://www.readbyqxmd.com/read/28513583/the-cohesin-like-recn-protein-stimulates-reca-mediated-recombinational-repair-of-dna-double-strand-breaks
#20
Lee A Uranga, Emigdio D Reyes, Praveen L Patidar, Lindsay N Redman, Shelley L Lusetti
RecN is a cohesin-like protein involved in DNA double-strand break repair in bacteria. The RecA recombinase functions to mediate repair via homologous DNA strand invasion to form D-loops. Here we provide evidence that the RecN protein stimulates the DNA strand invasion step of RecA-mediated recombinational DNA repair. The intermolecular DNA tethering activity of RecN protein described previously cannot fully explain this novel activity since stimulation of RecA function is species-specific and requires RecN ATP hydrolysis...
May 17, 2017: Nature Communications
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