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DNA damage chromosome translocation

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https://www.readbyqxmd.com/read/28685056/pml-silencing-inhibits-cell-proliferation-and-induces-dna-damage-in-cultured-ovarian-cancer-cells
#1
Sheng-Bing Liu, Zhong-Fei Shen, Yan-Jun Guo, Li-Xian Cao, Ying Xu
The promyelocytic leukemia (PML) gene is a tumor suppressor gene. It was first identified in acute promyelocytic leukemia, in which it is fused to retinoic acid receptor α by the (15;17) chromosomal translocation. The function of the PML protein is frequently lost or aberrant in human solid tumors. In human ovarian carcinoma tissue, PML detected by immunohistochemistry was highly expressed. A PML-silencing vector, pSRG-shPml, was constructed and used to transfect human ovarian cancer cells. Cells were cultured and selected with puromycin for 10-15 days, and then the PML mRNA expression levels were detected by RT-qPCR and immunofluorescence...
July 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28666258/peptide-microarray-profiling-identifies-phospholipase-c-gamma-1-plc-%C3%AE-1-as-a-potential-target-for-t-8-21-aml
#2
Hasan Mahmud, Frank J G Scherpen, Tiny Meeuwsen de Boer, Harm-Jan Lourens, Caroline Schoenherr, Matthias Eder, Michaela Scherr, Victor Guryev, Eveline S De Bont
The t(8;21) (q22;q22) chromosomal translocation is one of the most frequent genetic alterations in acute myeloid leukemia (AML) which has a need for improved therapeutic strategies. We found PLC-γ1 as one of the highest phosphorylated peptides in t(8;21) AML samples compared to NBM or CN-AML in our previous peptide microarray. PLC-γ1 is known to play a role in cancer progression, however, the impact of PLC-γ1 in AML is currently unknown. Therefore, we aimed to study the functional role of PLC-γ1 by investigating the cellular growth, survival and its underlying mechanism in t(8;21) AML...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28596964/oxidative-stress-induced-dna-damage-by-manganese-dioxide-nanoparticles-in-human-neuronal-cells
#3
Saud Alarifi, Daoud Ali, Saad Alkahtani
Metal nanoparticles have been extensively used in industry as well as in biomedical application. In this work, we have evaluated the toxic potential of manganese dioxide (MnO2) nanoparticles (MNPs) on human neuronal (SH-SY5Y) cells. Cellular toxicity due to MNPs (0, 10, 30, and 60 μg/ml) on the SH-SY5Y cell was observed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red uptake (NRU) tests. MNPs produced reactive oxygen species (ROS) and declined in mitochondrial membrane potential in the SH-SY5Y cell in dose and duration dependent manner...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28447610/parp3-is-a-promoter-of-chromosomal-rearrangements-and-limits-g4-dna
#4
Tovah A Day, Jacob V Layer, J Patrick Cleary, Srijoy Guha, Kristen E Stevenson, Trevor Tivey, Sunhee Kim, Anna C Schinzel, Francesca Izzo, John Doench, David E Root, William C Hahn, Brendan D Price, David M Weinstock
Chromosomal rearrangements are essential events in the pathogenesis of both malignant and nonmalignant disorders, yet the factors affecting their formation are incompletely understood. Here we develop a zinc-finger nuclease translocation reporter and screen for factors that modulate rearrangements in human cells. We identify UBC9 and RAD50 as suppressors and 53BP1, DDB1 and poly(ADP)ribose polymerase 3 (PARP3) as promoters of chromosomal rearrangements across human cell types. We focus on PARP3 as it is dispensable for murine viability and has druggable catalytic activity...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28411178/microrna-expression-profiling-of-xp11-renal-cell-carcinoma
#5
Luigi Marchionni, Masamichi Hayashi, Elisa Guida, Akira Ooki, Enrico Munari, Fayez J Jabboure, Wikum Dinalankara, Ali Raza, George J Netto, Mohammad O Hoque, Pedram Argani
Renal cell carcinomas (RCCs) with Xp11 translocation (Xp11 RCC) constitute a distinctive molecular subtype characterized by chromosomal translocations involving the Xp11.2 locus, resulting in gene fusions between the TFE3 transcription factor with a second gene (usually ASPSCR1, PRCC, NONO, or SFPQ). RCCs with Xp11 translocations comprise up to 1-4% of adult cases, frequently displaying papillary architecture with epithelioid clear cells. In order to better understand the biology of this molecularly distinct tumor subtype, we analyze the miRNA expression profiles of Xp11 Renal cell carcinoma (RCC) compared to normal renal parenchyma using microarray and quantitative reverse transcription polymerase chain reaction (RT-PCR)...
April 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/28360415/hiv-tat-induces-a-prolonged-myc-relocalization-next-to-igh-in-circulating-b-cells
#6
D Germini, T Tsfasman, M Klibi, R El-Amine, A Pichugin, O V Iarovaia, C Bilhou-Nabera, F Subra, Y Bou Saada, A Sukhanova, D Boutboul, M Raphaël, J Wiels, S V Razin, S Bury-Moné, E Oksenhendler, M Lipinski, Y S Vassetzky
With combined antiretroviral therapy (cART), the risk for HIV-infected individuals to develop a non-Hodgkin lymphoma is diminished. However, the incidence of Burkitt lymphoma (BL) remains strikingly elevated. Most BL present a t(8;14) chromosomal translocation which must take place at a time of spatial proximity between the translocation partners. The two partner genes, MYC and IGH, were found colocalized only very rarely in the nuclei of normal peripheral blood B-cells examined using 3D-FISH while circulating B-cells from HIV-infected individuals whose exhibited consistently elevated levels of MYC-IGH colocalization...
April 25, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28360097/chk2-overexpression-and-mislocalisation-within-mitotic-structures-enhances-chromosomal-instability-and-hepatocellular-carcinoma-progression
#7
Vinicio Carloni, Matteo Lulli, Stefania Madiai, Tommaso Mello, Andrew Hall, Tu Vinh Luong, Massimo Pinzani, Krista Rombouts, Andrea Galli
OBJECTIVE: Chromosomal instability (CIN) is the most common form of genomic instability, which promotes hepatocellular carcinoma (HCC) progression by enhancing tumour heterogeneity, drug resistance and immunity escape. CIN per se is an important factor of DNA damage, sustaining structural chromosome abnormalities but the underlying mechanisms are unknown. DESIGN: DNA damage response protein checkpoint kinase 2 (Chk2) expression was evaluated in an animal model of diethylnitrosamine-induced HCC characterised by DNA damage and elevated mitotic errors...
March 30, 2017: Gut
https://www.readbyqxmd.com/read/28270142/dynamic-proteomics-reveals-bimodal-protein-dynamics-of-cancer-cells-in-response-to-hsp90-inhibitor
#8
Anat Zimmer, Shlomit Amar-Farkash, Tamar Danon, Uri Alon
BACKGROUND: Drugs often kill some cancer cells while others survive. This stochastic outcome is seen even in clonal cells grown under the same conditions. Understanding the molecular reasons for this stochastic outcome is a current challenge, which requires studying the proteome at the single cell level over time. In a previous study we used dynamic proteomics to study the response of cancer cells to a DNA damaging drug, camptothecin. Several proteins showed bimodal dynamics: they rose in some cells and decreased in others, in a way that correlated with eventual cell fate: death or survival...
March 7, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28258182/annealing-of-complementary-dna-sequences-during-double-strand-break-repair-in-drosophila-is-mediated-by-the-ortholog-of-smarcal1
#9
Julie Korda Holsclaw, Jeff Sekelsky
DNA double-strand breaks (DSBs) pose a serious threat to genomic integrity. If unrepaired, they can lead to chromosome fragmentation and cell death. If repaired incorrectly, they can cause mutations and chromosome rearrangements. DSBs are repaired using end-joining or homology-directed repair strategies, with the predominant form of homology-directed repair being synthesis-dependent strand annealing (SDSA). SDSA is the first defense against genomic rearrangements and information loss during DSB repair, making it a vital component of cell health and an attractive target for chemotherapeutic development...
May 2017: Genetics
https://www.readbyqxmd.com/read/28213501/immature-lymphocytes-inhibit-rag1-and-rag2-transcription-and-v-d-j-recombination-in-response-to-dna-double-strand-breaks
#10
Megan R Fisher, Adrian Rivera-Reyes, Noah B Bloch, David G Schatz, Craig H Bassing
Mammalian cells have evolved a common DNA damage response (DDR) that sustains cellular function, maintains genomic integrity, and suppresses malignant transformation. In pre-B cells, DNA double-strand breaks (DSBs) induced at Igκ loci by the Rag1/Rag2 (RAG) endonuclease engage this DDR to modulate transcription of genes that regulate lymphocyte-specific processes. We previously reported that RAG DSBs induced at one Igκ allele signal through the ataxia telangiectasia mutated (ATM) kinase to feedback-inhibit RAG expression and RAG cleavage of the other Igκ allele...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28063109/mutation-screening-of-ackr3-and-cops8-in-kidney-cancer-cases-from-the-confirm-study
#11
Maryam Mahmoodi, Tu Nguyen-Dumont, Fleur Hammet, Bernard J Pope, Daniel J Park, Melissa C Southey, John M Darlow, Fiona Bruinsma, Ingrid Winship
An apparently balanced t(2;3)(q37.3;q13.2) translocation that appears to segregate with renal cell carcinoma (RCC) has indicated potential areas to search for the elusive genetic basis of clear cell RCC. We applied Hi-Plex targeted sequencing to analyse germline DNA from 479 individuals affected with clear cell RCC for this breakpoint translocation and genetic variants in neighbouring genes on chromosome 2, ACKR3 and COPS8. While only synonymous variants were found in COPS8, one of the missense variants in ACKR3:c...
January 6, 2017: Familial Cancer
https://www.readbyqxmd.com/read/27998928/the-cell-cycle-restricts-activation-induced-cytidine-deaminase-activity-to-early-g1
#12
Qiao Wang, Kyong-Rim Kieffer-Kwon, Thiago Y Oliveira, Christian T Mayer, Kaihui Yao, Joy Pai, Zhen Cao, Marei Dose, Rafael Casellas, Mila Jankovic, Michel C Nussenzweig, Davide F Robbiani
Activation-induced cytidine deaminase (AID) converts cytosine into uracil to initiate somatic hypermutation (SHM) and class switch recombination (CSR) of antibody genes. In addition, this enzyme produces DNA lesions at off-target sites that lead to mutations and chromosome translocations. However, AID is mostly cytoplasmic, and how and exactly when it accesses nuclear DNA remains enigmatic. Here, we show that AID is transiently in spatial contact with genomic DNA from the time the nuclear membrane breaks down in prometaphase until early G1, when it is actively exported into the cytoplasm...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27942359/cytolethal-distending-toxin-from-campylobacter-jejuni-requires-the-cytoskeleton-for-toxic-activity
#13
Estela T Méndez-Olvera, Jaime A Bustos-Martínez, Yolanda López-Vidal, Antonio Verdugo-Rodríguez, Daniel Martínez-Gómez
BACKGROUND: Campylobacter jejuni is one of the major causes of infectious diarrhea worldwide. The distending cytolethal toxin (CDT) of Campylobacter spp. interferes with normal cell cycle progression. This toxic effect is considered a result of DNase activity that produces chromosomal DNA damage. To perform this event, the toxin must be endocytosed and translocated to the nucleus. OBJECTIVES: The aim of this study was to evaluate the role of the cytoskeleton in the translocation of CDT to the nucleus...
October 2016: Jundishapur Journal of Microbiology
https://www.readbyqxmd.com/read/27939934/radiation-induced-clustered-dna-lesions-repair-and-mutagenesis
#14
REVIEW
Evelyne Sage, Naoya Shikazono
Clustered DNA lesions, also called Multiply Damaged Sites, is the hallmark of ionizing radiation. It is defined as the combination of two or more lesions, comprising strand breaks, oxidatively generated base damage, abasic sites within one or two DNA helix turns, created by the passage of a single radiation track. DSB clustered lesions associate DSB and several base damage and abasic sites in close vicinity, and are assimilated to complex DSB. Non-DSB clustered lesions comprise single strand break, base damage and abasic sites...
June 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27888607/catastrophic-cellular-events-leading-to-complex-chromosomal-rearrangements-in-the-germline
#15
REVIEW
M Fukami, H Shima, E Suzuki, T Ogata, K Matsubara, T Kamimaki
Although complex chromosomal rearrangements were thought to reflect the accumulation of DNA damage over time, recent studies have shown that such rearrangements frequently arise from 'all-at-once' catastrophic cellular events. These events, designated chromothripsis, chromoanasynthesis, and chromoanagenesis, were first documented in the cancer genome and subsequently observed in the germline. These events likely result from micronucleus-mediated chromosomal shattering and subsequent random reassembly of DNA fragments, although several other mechanisms have also been proposed...
May 2017: Clinical Genetics
https://www.readbyqxmd.com/read/27769161/growth-conditions-that-increase-or-decrease-lifespan-in-saccharomyces-cerevisiae-lead-to-corresponding-decreases-or-increases-in-rates-of-interstitial-deletions-and-non-reciprocal-translocations
#16
Patrick H Maxwell
BACKGROUND: Accumulation of DNA damage, mutations, and chromosomal abnormalities is associated with aging in many organisms. How directly various forms of genomic instability contribute to lifespan in different aging contexts is still under active investigation. Testing whether treatments that alter lifespan change mutation rates early during lifespan could provide support for genomic instability being at least partly responsible for changes in the rates of aging. RESULTS: Rates of mutations, direct repeat recombination, or retrotransposition were measured in young cell populations from two strain backgrounds of Saccharomyces cerevisiae exposed to several growth conditions that shortened or extended yeast chronological lifespan...
October 21, 2016: BMC Genetics
https://www.readbyqxmd.com/read/27711078/attenuated-dna-damage-repair-delays-therapy-related-myeloid-neoplasms-in-a-mouse-model
#17
Kit I Tong, Kazushige Ota, Akiyoshi Komuro, Takeshi Ueda, Akihiko Ito, C Anne Koch, Hitoshi Okada
Therapy-related cancers are potentially fatal late life complications for patients who received radio- or chemotherapy. So far, the mouse model showing reduction or delay of these diseases has not been described. We found that the disruption of Aplf in mice moderately attenuated DNA damage repair and, unexpectedly, impeded myeloid neoplasms after exposure to ionizing radiation (IR). Irradiated mutant mice showed higher rates of p53-dependent cell death, fewer chromosomal translocations, and a delay in malignancy-induced mortality...
October 6, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27667193/satellite-rnas-promote-pancreatic-oncogenic-processes-via-the-dysfunction-of-ybx1
#18
Takahiro Kishikawa, Motoyuki Otsuka, Takeshi Yoshikawa, Motoko Ohno, Hideaki Ijichi, Kazuhiko Koike
Highly repetitive tandem arrays at the centromeric and pericentromeric regions in chromosomes, previously considered silent, are actively transcribed, particularly in cancer. This aberrant expression occurs even in K-ras-mutated pancreatic intraepithelial neoplasia (PanIN) tissues, which are precancerous lesions. To examine the biological roles of the satellite RNAs in carcinogenesis, we construct mouse PanIN-derived cells expressing major satellite (MajSAT) RNA and show increased malignant properties. We find an increase in frequency of chromosomal instability and point mutations in both genomic and mitochondrial DNA...
September 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27559048/the-dna-damage-response-regulates-rag1-2-expression-in-pre-b-cells-through-atm-foxo1-signaling
#19
Katarina Ochodnicka-Mackovicova, Mahnoush Bahjat, Chiel Maas, Amélie van der Veen, Timon A Bloedjes, Alexander M de Bruin, Harmen van Andel, Carol E Schrader, Rudi W Hendriks, Els Verhoeyen, Richard J Bende, Carel J M van Noesel, Jeroen E J Guikema
The recombination activating gene (RAG) 1 and RAG2 protein complex introduces DNA breaks at Tcr and Ig gene segments that are required for V(D)J recombination in developing lymphocytes. Proper regulation of RAG1/2 expression safeguards the ordered assembly of Ag receptors and the development of lymphocytes, while minimizing the risk for collateral damage. The ataxia telangiectasia mutated (ATM) kinase is involved in the repair of RAG1/2-mediated DNA breaks and prevents their propagation. The simultaneous occurrence of RAG1/2-dependent and -independent DNA breaks in developing lymphocytes exposed to genotoxic stress increases the risk for aberrant recombinations...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27558650/topology-of-chromosome-centromeres-in-human-sperm-nuclei-with-high-levels-of-dna-damage
#20
Ewa Wiland, Monika Fraczek, Marta Olszewska, Maciej Kurpisz
Several studies have shown that the 'poor' sperm DNA quality appears to be an important factor affecting male reproductive ability. In the case of sperm cells from males with the correct somatic karyotype but with deficient spermatogenesis, resulting in a high degree of sperm DNA fragmentation, we observed changes in the preferential topology of the chromosome 7, 9, 15, 18, X and Y centromeres. The changes occurred in radial localization and may have been directly linked to the sperm chromatin damage. This conclusion is mainly based on a comparison of FISH signals that were observed simultaneously in the TUNEL-positive and TUNEL-negative sperm cells...
2016: Scientific Reports
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