keyword
MENU ▼
Read by QxMD icon Read
search

Ku70

keyword
https://www.readbyqxmd.com/read/28974511/tox-regulates-growth-dna-repair-and-genomic-instability-in-t-cell-acute-lymphoblastic-leukemia
#1
Riadh Lobbardi, Jordan Pinder, Barbara Martinez-Pastor, Marina Theodorou, Jessica S Blackburn, Brian J Abraham, Yuka Namiki, Marc Mansour, Nouran S Abdelfattah, Aleksey Molodtsov, Gabriela Alexe, Debra Toiber, Manon de Waard, Esha Jain, Myriam Boukhali, Mattia Lion, Deepak Bhere, Khalid Shah, Alejandro Gutierrez, Kimberly Stegmaier, Lewis B Silverman, Ruslan I Sadreyev, John M Asara, Marjorie A Oettinger, Wilhelm Haas, A Thomas Look, Richard A Young, Raul Mostoslavsky, Graham Dellaire, David M Langenau
T-cell Acute Lymphoblastic Leukemia (T-ALL) is an aggressive malignancy of thymocytes. Using a transgenic screen in zebrafish, thymocyte selection-associated high mobility box protein (TOX) was uncovered as a collaborating oncogenic driver that accelerated T-ALL onset by expanding the initiating pool of transformed clones and elevating genomic instability. TOX is highly expressed in a majority of human T-ALL and is required for proliferation and continued xenograft growth in mice. Using a wide array of functional analyses, we uncovered that TOX binds directly to KU70/80 and suppresses recruitment of this complex to DNA breaks to inhibit Non-Homologous End Joining repair (NHEJ)...
October 3, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28959974/regulation-of-dna-repair-pathway-choice-in-s-and-g2-phases-by-the-nhej-inhibitor-cyren
#2
Nausica Arnoult, Adriana Correia, Jiao Ma, Anna Merlo, Sara Garcia-Gomez, Marija Maric, Marco Tognetti, Christopher W Benner, Simon J Boulton, Alan Saghatelian, Jan Karlseder
Classical non-homologous end joining (cNHEJ) and homologous recombination compete for the repair of double-stranded DNA breaks during the cell cycle. Homologous recombination is inhibited during the G1 phase of the cell cycle, but both pathways are active in the S and G2 phases. However, it is unclear why cNHEJ does not always outcompete homologous recombination during the S and G2 phases. Here we show that CYREN (cell cycle regulator of NHEJ) is a cell-cycle-specific inhibitor of cNHEJ. Suppression of CYREN allows cNHEJ to occur at telomeres and intrachromosomal breaks during the S and G2 phases, and cells lacking CYREN accumulate chromosomal aberrations upon damage induction, specifically outside the G1 phase...
September 20, 2017: Nature
https://www.readbyqxmd.com/read/28948410/protective-molecular-mechanisms-of-clusterin-against-apoptosis-in-cardiomyocytes
#3
REVIEW
Rodrigo Martins Pereira, Rania A Mekary, Kellen Cristina da Cruz Rodrigues, Chadi Pellegrini Anaruma, Eduardo Rochete Ropelle, Adelino Sanchez Ramos da Silva, Dennys Esper Cintra, José Rodrigo Pauli, Leandro Pereira de Moura
Loss of cardiomyocytes occurs with aging and contributes to cardiovascular complications. In the present study, we highlighted the role of clusterin, a protein that has recently been associated with the protection of cardiomyocytes from apoptosis. Clusterin protects cardiac cells against damage from myocardial infarction, transplant, or myocarditis. Clusterin can act directly or indirectly on apoptosis by regulating several intracellular pathways. These pathways include (1) the oxidant and inflammatory program, (2) insulin growth factor 1 (IGF-1) pathway, (3) KU70 / BCL-2-associated X protein (BAX) pathway, (4) tumor necrosis factor alpha (TNF-α) pathway, (5) BCL-2 antagonist of cell death (BAD) pathway, and (6) mitogen-activated protein kinase (MAPK) pathway...
September 25, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/28927087/gimeracil-enhances-the-antitumor-effect-of-cisplatin-in-oral-squamous-cell-carcinoma-cells-in-vitro-and-in-vivo
#4
Koji Harada, Tarannum Ferdous, Toyoko Harada, Takanori Takenawa, Yoshiya Ueyama
Gimeracil or 5-chloro-2,4-dihydroxypyridine (CDHP) enhances the antitumor effects of 5-fluorouracil (5-FU) by inhibiting dihydropyrimidine dehydrogenase (DPD), which is involved in the degradation of 5-FU. CDHP, as part of a combination therapy, was also reported to exert a radiosensitizing effect. Therefore, CDHP may have underlying mechanisms of action other than DPD inhibition. The focus of the present study was to investigate the antitumor effects of CDHP and cisplatin (CDDP) combination treatment in vitro and in vivo against oral squamous cell carcinoma (OSCC) tumors...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28925388/structural-step-forward-for-nhej
#5
Go Watanabe, Michael R Lieber, Dewight Williams
In a recent paper published in Cell Research, a cryo-EM structure reveals the interface between DNA-PKcs and the Ku70/80:DNA complex, together forming the DNA-dependent protein kinase holoenzyme in non-homologous DNA end joining. Insight from this structure suggests how an allosteric rearrangement of DNA-PKcs driven by Ku70/80:DNA binding regulates kinase activity in this largest member of a family of structurally homologous phosphoinositide 3-kinase-related protein kinases that includes mTOR, ATR, and ATM.
September 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28867292/single-molecule-imaging-reveals-how-mre11-rad50-nbs1-initiates-dna-break-repair
#6
Logan R Myler, Ignacio F Gallardo, Michael M Soniat, Rajashree A Deshpande, Xenia B Gonzalez, Yoori Kim, Tanya T Paull, Ilya J Finkelstein
DNA double-strand break (DSB) repair is essential for maintaining our genomes. Mre11-Rad50-Nbs1 (MRN) and Ku70-Ku80 (Ku) direct distinct DSB repair pathways, but the interplay between these complexes at a DSB remains unclear. Here, we use high-throughput single-molecule microscopy to show that MRN searches for free DNA ends by one-dimensional facilitated diffusion, even on nucleosome-coated DNA. Rad50 binds homoduplex DNA and promotes facilitated diffusion, whereas Mre11 is required for DNA end recognition and nuclease activities...
September 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28860152/proteasome-inhibitor-bortezomib-is-a-novel-therapeutic-agent-for-focal-radiation-induced-osteoporosis
#7
Abhishek Chandra, Luqiang Wang, Tiffany Young, Leilei Zhong, Wei-Ju Tseng, Michael A Levine, Keith Cengel, X Sherry Liu, Yejia Zhang, Robert J Pignolo, Ling Qin
Bone atrophy and its related fragility fractures are frequent, late side effects of radiotherapy in cancer survivors and have a detrimental impact on their quality of life. In another study, we showed that parathyroid hormone 1-34 and anti-sclerostin antibody attenuates radiation-induced bone damage by accelerating DNA repair in osteoblasts. DNA damage responses are partially regulated by the ubiquitin proteasome pathway. In the current study, we examined whether proteasome inhibitors have similar bone-protective effects against radiation damage...
August 31, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28855246/localisation-of-double-strand-break-repair-proteins-to-viral-replication-compartments-following-lytic-reactivation-of-kshv
#8
Robert Hollingworth, Richard D Horniblow, Calum Forrest, Grant S Stewart, Roger J Grand
Double-strand breaks (DSBs) in DNA are recognised by the Ku70/80 heterodimer and the MRE11-RAD50-NBS1 (MRN) complex and result in activation of the DNA-PK and ATM kinases that play key roles in regulating the cellular DNA damage response (DDR). DNA tumour viruses such as Kaposi's sarcoma-associated herpesvirus (KSHV) are known to interact extensively with the DDR during the course of their replicative cycles. Here we show that during lytic amplification of KSHV DNA, the Ku70/80 heterodimer and the MRN complex consistently co-localise with viral genomes in replication compartments (RCs) whereas other DSB repair proteins form foci outside of RCs...
August 30, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28840859/cryo-em-structure-of-human-dna-pk-holoenzyme
#9
Xiaotong Yin, Mengjie Liu, Yuan Tian, Jiawei Wang, Yanhui Xu
DNA-dependent protein kinase (DNA-PK) is a serine/threonine protein kinase complex composed of a catalytic subunit (DNA-PKcs) and KU70/80 heterodimer bound to DNA. DNA-PK holoenzyme plays a critical role in non-homologous end joining (NHEJ), the major DNA repair pathway. Here, we determined cryo-electron microscopy structure of human DNA-PK holoenzyme at 6.6 Å resolution. In the complex structure, DNA-PKcs, KU70, KU80 and DNA duplex form a 650-kDa heterotetramer with 1:1:1:1 stoichiometry. The N-terminal α-solenoid (∼2 800 residues) of DNA-PKcs adopts a double-ring fold and connects the catalytic core domain of DNA-PKcs and KU70/80-DNA...
August 25, 2017: Cell Research
https://www.readbyqxmd.com/read/28832943/crispri-repression-of-nonhomologous-end-joining-for-enhanced-genome-engineering-via-homologous-recombination-in-yarrowia-lipolytica
#10
Cory Schwartz, Keith Frogue, Adithya Ramesh, Joshua Misa, Ian Wheeldon
In many organisms of biotechnological importance precise genome editing is limited by inherently low homologous recombination (HR) efficiencies. A number of strategies exist to increase the effectiveness of this native DNA repair pathway; however, most strategies rely on permanently disabling competing repair pathways, thus reducing an organism's capacity to repair naturally occurring double strand breaks. Here, we describe a CRISPR interference (CRISPRi) system for gene repression in the oleochemical-producing yeast Yarrowia lipolytica...
August 19, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28821586/ku70-senses-htlv-1-dna-and-modulates-htlv-1-replication
#11
Jie Wang, Lixia Kang, Di Song, Lu Liu, Shuai Yang, Lingling Ma, Zhixiang Guo, Huaxia Ding, Hui Wang, Bo Yang
Human T lymphotropic virus type 1 (HTLV-1) belongs to the deltaretrovirus family and has been linked to multiple diseases. However, the innate host defense against HTLV-1 is unclear. In this study, we report that the expression of Ku70, a known DNA sensor against DNA viruses, could be induced by HTLV-1 infection in HeLa, PMA-differentiated THP1 cells, primary human monocytes, and human monocyte-derived macrophages. In these cells, the overexpression of Ku70 inhibited the HTLV-1 protein expression, whereas the knockdown of Ku70 promoted the HTLV-1 protein expression...
August 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28794690/gender-related-prognostic-significance-of-clinical-and-biological-tumor-features-in-rectal-cancer-patients-receiving-short-course-preoperative-radiotherapy
#12
Anna Gasinska, Zbigniew Darasz, Agnieszka Adamczyk, Beata Biesaga, Joanna Niemiec, Marian Reinfuss
AIM: To study the prognostic value of clinical and biological features of rectal cancer and potential gender differences in patients' overall survival (OS), local recurrence-free survival (RFS) and metastasis-free survival (MFS) after short-course preoperative radiotherapy (SCRT) with short or long interval between RT and surgery (break). BACKGROUND: The length of the interval between RT and surgery in SCRT is debatable and gender-related differences in patients survival are not established yet...
September 2017: Reports of Practical Oncology and Radiotherapy
https://www.readbyqxmd.com/read/28780472/different-profiles-of-the-mrna-levels-of-dna-repair-genes-in-mcf-7-and-sh-sy5y-cells-after-treatment-with-combination-of-cisplatin-50-hz-electromagnetic-field-and-bleomycin
#13
Fatemeh Sanie-Jahromi, Mostafa Saadat
Neurotoxicity is known to be a major dose-limiting adverse effect of cisplatin (CDDP), alone or in combination with other chemicals. DNA repair capacity serve as a neuroprotective factor against CDDP. The purpose of this study was to evaluate the effect of 50-Hz electromagnetic field (EMF) in combination with CDDP and bleomycin (Bleo) on expression of some of DNA repair genes (GADD45A, XRCC1, XRCC4, Ku70, Ku80, DNA-PKcs and LIG4) in MCF-7 (breast cancer) and SH-SY5Y (neuroblastoma) cell lines. MCF-7 and SH-SY5Y cells were pre-treated with CDDP in the presence or absence of EMF and then exposed to different concentration of Bleo...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28759779/synthetic-lethality-between-murine-dna-repair-factors-xlf-and-dna-pkcs-is-rescued-by-inactivation-of-ku70
#14
Mengtan Xing, Magnar Bjørås, Jeremy A Daniel, Frederick W Alt, Valentyn Oksenych
DNA double-strand breaks (DSBs) are recognized and repaired by the Classical Non-Homologous End-Joining (C-NHEJ) and Homologous Recombination pathways. C-NHEJ includes the core Ku70 and Ku80 (or Ku86) heterodimer that binds DSBs and thus promotes recruitment of accessory downstream NHEJ factors XLF, PAXX, DNA-PKcs, Artemis and other core subunits, XRCC4 and DNA Ligase 4 (Lig4). In the absence of core C-NHEJ factors, DNA repair can be performed by Alternative End-Joining, which likely depends on DNA Ligase 1 and DNA Ligase 3...
September 2017: DNA Repair
https://www.readbyqxmd.com/read/28720717/sting-is-an-essential-mediator-of-the-ku70-mediated-production-of-ifn-%C3%AE-1-in-response-to-exogenous-dna
#15
Hongyan Sui, Ming Zhou, Hiromi Imamichi, Xiaoli Jiao, Brad T Sherman, H Clifford Lane, Tomozumi Imamichi
We previously identified Ku70, a subunit of a DNA repair protein complex, as a cytosolic DNA sensor that induces the production of interferon-λ1 (IFN-λ1) by human primary cells and cell lines. IFN-λ1 is a type III IFN and has similar antiviral activity to that of the type I IFNs (IFN-α and IFN-β). We observed that human embryonic kidney (HEK) 293T cells, which are deficient in the innate immune adaptor protein STING (stimulator of IFN genes), did not produce IFN-λ1 in response to DNA unless they were reconstituted with STING...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28717247/characterization-of-hiv-1-integrase-interaction-with-human-ku70-protein-and-initial-implications-for-drug-targeting
#16
Andrey N Anisenko, Ekaterina S Knyazhanskaya, Artur O Zalevsky, Julia Yu Agapkina, Aleksander I Sizov, Timofey S Zatsepin, Marina B Gottikh
Human Ku70/Ku80 protein is known to influence HIV-1 replication. One of the possible reasons may be the protection of integrase from proteasomal degradation by Ku70 subunit. We demonstrated that recombinant HIV-1 integrase and Ku70 form a stable complex, while no interaction of Ku70 with integrase from prototype foamy virus was observed. By analyzing protein subdomains we determined two binding sites in the structure of both Ku70 and integrase: the 51-160 a.a. region of integrase interacts with residues 251-438 of Ku70, whereas Ku70 N-terminal domain (1-250 a...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28712728/hexim1-and-neat1-long-non-coding-rna-form-a-multi-subunit-complex-that-regulates-dna-mediated-innate-immune-response
#17
Mehdi Morchikh, Alexandra Cribier, Raoul Raffel, Sonia Amraoui, Julien Cau, Dany Severac, Emeric Dubois, Olivier Schwartz, Yamina Bennasser, Monsef Benkirane
The DNA-mediated innate immune response underpins anti-microbial defenses and certain autoimmune diseases. Here we used immunoprecipitation, mass spectrometry, and RNA sequencing to identify a ribonuclear complex built around HEXIM1 and the long non-coding RNA NEAT1 that we dubbed the HEXIM1-DNA-PK-paraspeckle components-ribonucleoprotein complex (HDP-RNP). The HDP-RNP contains DNA-PK subunits (DNAPKc, Ku70, and Ku80) and paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATRIN3). We show that binding of HEXIM1 to NEAT1 is required for its assembly...
August 3, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28674407/hdac6-a-novel-histone-deacetylase-implicated-in-pulmonary-arterial-hypertension
#18
Olivier Boucherat, Sophie Chabot, Roxane Paulin, Isabelle Trinh, Alice Bourgeois, François Potus, Marie-Claude Lampron, Caroline Lambert, Sandra Breuils-Bonnet, Valérie Nadeau, Renée Paradis, Elena A Goncharova, Steeve Provencher, Sébastien Bonnet
Pulmonary arterial hypertension (PAH) is a vascular remodeling disease with limited therapeutic options. Although exposed to stressful conditions, pulmonary artery (PA) smooth muscle cells (PASMCs) exhibit a "cancer-like" pro-proliferative and anti-apoptotic phenotype. HDAC6 is a cytoplasmic histone deacetylase regulating multiple pro-survival mechanisms and overexpressed in response to stress in cancer cells. Due to the similarities between cancer and PAH, we hypothesized that HDAC6 expression is increased in PAH-PASMCs to face stress allowing them to survive and proliferate, thus contributing to vascular remodeling in PAH...
July 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28657072/development-of-a-crispr-cas9-system-for-efficient-genome-editing-of-candida-lusitaniae
#19
Emily L Norton, Racquel K Sherwood, Richard J Bennett
Candida lusitaniae is a member of the Candida clade that includes a diverse group of fungal species relevant to both human health and biotechnology. This species exhibits a full sexual cycle to undergo interconversion between haploid and diploid forms. C. lusitaniae is also an emerging opportunistic pathogen that can cause serious bloodstream infections in the clinic and yet has often proven to be refractory to facile genetic manipulations. In this work, we develop a clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated gene 9 (Cas9) system to enable genome editing of C...
May 2017: MSphere
https://www.readbyqxmd.com/read/28652322/cryo-em-structure-of-the-dna-pk-holoenzyme
#20
Humayun Sharif, Yang Li, Yuanchen Dong, Liyi Dong, Wei Li Wang, Youdong Mao, Hao Wu
DNA-dependent protein kinase (DNA-PK) is a large protein complex central to the nonhomologous end joining (NHEJ) DNA-repair pathway. It comprises the DNA-PK catalytic subunit (DNA-PKcs) and the heterodimer of DNA-binding proteins Ku70 and Ku80. Here, we report the cryo-electron microscopy (cryo-EM) structures of human DNA-PKcs at 4.4-Å resolution and the DNA-PK holoenzyme at 5.8-Å resolution. The DNA-PKcs structure contains three distinct segments: the N-terminal region with an arm and a bridge, the circular cradle, and the head that includes the kinase domain...
July 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
keyword
keyword
48114
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"