keyword
MENU ▼
Read by QxMD icon Read
search

non-homologous end-joining

keyword
https://www.readbyqxmd.com/read/28228480/a-stable-but-reversible-integrated-surrogate-reporter-for-assaying-crispr-cas9-stimulated-homology-directed-repair
#1
Yahong Wen, Grace Liao, Thomas Pritchard, Ting-Ting Zhao, Jon P Connelly, Shondra M Pruett-Miller, Valerie Blanc, Nicholas O Davidson, Blair B Madison
The discovery and application of CRISPR/Cas9 technology for genome editing has greatly accelerated targeted mutagenesis in a variety of organisms. CRISPR/Cas9-mediated site-specific cleavage is typically exploited for the generation of insertions or deletions (indels) following aberrant dsDNA repair via the endogenous non-homology end-joining (NHEJ) pathway, or alternatively, for enhancing homology directed repair (HDR) to facilitate the generation of a specific mutation (or knock-in). However, there is a need for efficient cellular assays that can measure Cas9/guide RNA (gRNA) activity...
February 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28226772/computational-analysis-of-androgen-receptor-dependent-radiosensitivity-in-prostate-cancer
#2
Mengdi Qian, Alexandru Almasan, Evren Gurkan-Cavusoglu, Mengdi Qian, Alexandru Almasan, Evren Gurkan-Cavusoglu, Mengdi Qian, Evren Gurkan-Cavusoglu, Alexandru Almasan
In this study, we quantitatively analyze the mechanism by which androgen deprivation therapy (ADT) is enhancing radiosensitivity in prostate cancer (PCa) patients. It has been shown in laboratory experiments, as well as in patient data in the literature, that the androgen receptor (AR) reduces the effectiveness of ionizing radiation treatment by enhancing the non-homologous end joining (NHEJ) repair of radiation damage. The suppression of AR by ADT suppresses the activity of NHEJ that leads to radiosensitivity in PCa patients...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28220186/efficient-gene-targeting-in-non-homologous-end-joining-deficient-lipomyces-starkeyi-strains
#3
Yoshifumi Oguro, Harutake Yamazaki, Satoshi Ara, Yosuke Shida, Wataru Ogasawara, Masamichi Takagi, Hiroaki Takaku
Microbial lipids are sustainable feedstock for the production of oleochemicals and biodiesel. Oleaginous yeasts have recently been proposed as alternative lipid producers to plants and animals to promote sustainability in the chemical and fuel industries. The oleaginous yeast Lipomyces starkeyi has great industrial potential as an excellent lipid producer. However, improvement of its lipid productivity is essential for the cost-effective production of oleochemicals and fuels. Genetic and metabolic engineering of L...
February 20, 2017: Current Genetics
https://www.readbyqxmd.com/read/28212417/splitax-a-novel-method-to-assess-the-function-of-engineered-nucleases
#4
Richard A Axton, Sharmin S Haideri, Martha Lopez-Yrigoyen, Helen A Taylor, Lesley M Forrester
Engineered nucleases have been used to generate knockout or reporter cell lines and a range of animal models for human disease. These new technologies also hold great promise for therapeutic genome editing. Current methods to evaluate the activity of these nucleases are time consuming, require extensive optimization and are hampered by readouts with low signals and high background. We have developed a simple and easy to perform method (SplitAx) that largely addresses these issues and provides a readout of nuclease activity...
2017: PloS One
https://www.readbyqxmd.com/read/28211977/1q21-3-deletion-involving-gatad2b-an-emerging-recurrent-microdeletion-syndrome
#5
Thipwimol Tim-Aroon, Natini Jinawath, Weerin Thammachote, Praweena Sinpitak, Anchalee Limrungsikul, Chaiyos Khongkhatithum, Duangrurdee Wattanasirichaigoon
GATAD2B gene is involved in chromatin modification and transcription activity. Loss-of-function mutations of GATAD2B have recently been defined to cause a recognizable syndrome with intellectual disability (ID). Human TPM3 gene encoding thin filament protein is associated with myopathies. Both genes are located on chromosome 1q21.3. We herein report an infant with feeding difficulty, developmental delay, hypotonia, and dysmorphic features including small palpebral fissures, telecanthus, sparse hair and eyebrow, cup-shaped ears, and clinodactyly...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28208769/localisation-microscopy-of-breast-epithelial-erbb-2-receptors-and-gap-junctions-trafficking-after-%C3%AE-irradiation-neuregulin-1%C3%AE-and-trastuzumab-application
#6
Götz Pilarczyk, Ines Nesnidal, Manuel Gunkel, Margund Bach, Felix Bestvater, Michael Hausmann
In cancer, vulnerable breast epithelium malignance tendency correlates with number and activation of ErbB receptor tyrosine kinases. In the presented work, we observe ErbB receptors activated by irradiation-induced DNA injury or neuregulin- 1 β application, or alternatively, attenuated by a therapeutic antibody using high resolution fluorescence localization microscopy. The gap junction turnover coinciding with ErbB receptor activation and co-transport is simultaneously recorded. DNA injury caused by 4 Gray of 6 MeV photon γ -irradiation or alternatively neuregulin- 1 β application mobilized ErbB receptors in a nucleograde fashion-a process attenuated by trastuzumab antibody application...
February 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207808/autologous-hematopoietic-stem-cell-transplantation-in-lymphoma-patients-is-associated-with-a-decrease-in-the-double-strand-break-repair-capacity-of-peripheral-blood-lymphocytes
#7
Sandrine Lacoste, Smita Bhatia, Yanjun Chen, Ravi Bhatia, Timothy R O'Connor
Patients who undergo autologous hematopoietic stem cell transplantation (aHCT) for treatment of a relapsed or refractory lymphoma are at risk of developing therapy related- myelodysplasia/acute myeloid leukemia (t-MDS/AML). Part of the risk likely resides in inherent interindividual differences in their DNA repair capacity (DRC), which is thought to influence the effect chemotherapeutic treatments have on the patient's stem cells prior to aHCT. Measuring DRC involves identifying small differences in repair proficiency among individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28188619/generation-of-conditional-oncogenic-chromosomal-translocations-using-crispr-cas9-genomic-editing-and-homology-directed-repair
#8
Lee Spraggon, Luciano G Martelotto, Julija Hmeljak, Tyler D Hitchman, Jiang Wang, Lu Wang, Emily K Slotkin, Pang-Dian Fan, Jorge S Reis-Filho, Marc Ladanyi
Chromosomal rearrangements encoding oncogenic fusion proteins are found in a wide variety of malignancies. The use of programmable nucleases to generate specific double-strand breaks in endogenous loci, followed by non-homologous end joining DNA repair, has allowed several of these translocations to be generated as constitutively expressed fusion genes within a cell population. Here, we describe a novel approach that combines CRISPR-Cas9 technology with homology-directed repair to engineer, capture and modulate the expression of chromosomal translocation products in a human cell line...
February 11, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28186989/inhibiting-dna-pkcs-in-a-non-homologous-end-joining-pathway-in-response-to-dna-double-strand-breaks
#9
Jun Dong, Tian Zhang, Yufeng Ren, Zhenyu Wang, Clifton C Ling, Fuqiu He, Gloria C Li, Chengtao Wang, Bixiu Wen
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a distinct factor in the non-homologous end-joining (NHEJ) pathway involved in DNA double-strand break (DSB) repair. We examined the crosstalk between key proteins in the DSB NHEJ repair pathway and cell cycle regulation and found that mouse embryonic fibroblast (MEF) cells deficient in DNA-PKcs or Ku70 were more vulnerable to ionizing radiation (IR) compared with wild-type cells and that DSB repair was delayed. γH2AX was associated with phospho-Ataxia-telangiectasia mutated kinase (Ser1987) and phospho-checkpoint effector kinase 1 (Ser345) foci for the arrest of cell cycle through the G2/M phase...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28179977/programmable-genome-editing-tools-and-their-regulation-for-efficient-genome-engineering
#10
REVIEW
Tuhin Kumar Guha, Alvan Wai, Georg Hausner
Targeted genome editing has become a powerful genetic tool for studying gene function or for modifying genomes by correcting defective genes or introducing genes. A variety of reagents have been developed in recent years that can generate targeted double-stranded DNA cuts which can be repaired by the error-prone, non-homologous end joining repair system or via the homologous recombination-based double-strand break repair pathway provided a suitable template is available. These genome editing reagents require components for recognizing a specific DNA target site and for DNA-cleavage that generates the double-stranded break...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/28177771/precision-genome-editing-in-the-crispr-era
#11
Jayme Salsman, Graham Dellaire
With the introduction of precision genome editing using CRISPR/Cas9 technology, we have entered a new era of genetic engineering and gene therapy. With RNA-guided endonucleases, such as Cas9, it is possible to engineer DNA double strand breaks (DSB) at specific genomic loci. DSB repair by the error-prone non-homologous end joining (NHEJ) pathway can disrupt a target gene by generating insertions and deletions. Alternatively, Cas9-mediated DSBs can be repaired by homology directed repair (HDR) using a homologous DNA repair template, thus allowing precise gene editing by incorporating genetic changes into the repair template...
September 29, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28167937/antiviral-defenses-in-plants-through-genome-editing
#12
REVIEW
Gustavo Romay, Claude Bragard
Plant-virus interactions based-studies have contributed to increase our understanding on plant resistance mechanisms, providing new tools for crop improvement. In the last two decades, RNA interference, a post-transcriptional gene silencing approach, has been used to induce antiviral defenses in plants with the help of genetic engineering technologies. More recently, the new genome editing systems (GES) are revolutionizing the scope of tools available to confer virus resistance in plants. The most explored GES are zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats/Cas9 endonuclease...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28163277/cloning-localization-and-focus-formation-at-dna-damage-sites-of-canine-ku70
#13
Manabu Koike, Yasutomo Yutoku, Aki Koike
Understanding the molecular mechanisms of DNA double-strand break (DSB) repair machinery, specifically non-homologous DNA-end joining (NHEJ), is crucial for developing next-generation radiotherapies and common chemotherapeutics for human and animal cancers. The localization, protein-protein interactions and post-translational modifications of core NHEJ factors, might play vital roles for regulation of NHEJ activity. The human Ku heterodimer (Ku70/Ku80) is a core NHEJ factor in the NHEJ pathway and is involved in sensing of DSBs...
February 6, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28138868/combination-treatment-using-ddx3-and-parp-inhibitors-induces-synthetic-lethality-in-brca1-proficient-breast-cancer
#14
Marise R Heerma van Voss, Justin D Brilliant, Farhad Vesuna, Guus M Bol, Elsken van der Wall, Paul J van Diest, Venu Raman
Triple-negative breast cancers have unfavorable outcomes due to their inherent aggressive behavior and lack of targeted therapies. Breast cancers occurring in BRCA1 mutation carriers are mostly triple-negative and harbor homologous recombination deficiency, sensitizing them to inhibition of a second DNA damage repair pathway by, e.g., PARP inhibitors. Unfortunately, resistance against PARP inhibitors in BRCA1-deficient cancers is common and sensitivity is limited in BRCA1-proficient breast cancers. RK-33, an inhibitor of the RNA helicase DDX3, was previously demonstrated to impede non-homologous end-joining repair of DNA breaks...
March 2017: Medical Oncology
https://www.readbyqxmd.com/read/28133776/non-homologous-end-joining-common-interaction-sites-and-exchange-of-multiple-factors-in-the-dna-repair-process
#15
Stuart L Rulten, Gabrielle J Grundy
Non-homologous end-joining (NHEJ) is the dominant means of repairing chromosomal DNA double strand breaks (DSBs), and is essential in human cells. Fifteen or more proteins can be involved in the detection, signalling, synapsis, end-processing and ligation events required to repair a DSB, and must be assembled in the confined space around the DNA ends. We review here a number of interaction points between the core NHEJ components (Ku70, Ku80, DNA-PKcs, XRCC4 and Ligase IV) and accessory factors such as kinases, phosphatases, polymerases and structural proteins...
January 30, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28132842/dna-double-strand-break-resection-occurs-during-non-homologous-end-joining-in-g1-but-is-distinct-from-resection-during-homologous-recombination
#16
Ronja Biehs, Monika Steinlage, Olivia Barton, Szilvia Juhász, Julia Künzel, Julian Spies, Atsushi Shibata, Penny A Jeggo, Markus Löbrich
Canonical non-homologous end joining (c-NHEJ) repairs DNA double-strand breaks (DSBs) in G1 cells with biphasic kinetics. We show that DSBs repaired with slow kinetics, including those localizing to heterochromatic regions or harboring additional lesions at the DSB site, undergo resection prior to repair by c-NHEJ and not alt-NHEJ. Resection-dependent c-NHEJ represents an inducible process during which Plk3 phosphorylates CtIP, mediating its interaction with Brca1 and promoting the initiation of resection. Mre11 exonuclease, EXD2, and Exo1 execute resection, and Artemis endonuclease functions to complete the process...
January 25, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28130555/xpf-knockout-via-crispr-cas9-reveals-that-ercc1-is-retained-in-the-cytoplasm-without-its-heterodimer-partner-xpf
#17
Janin Lehmann, Christina Seebode, Sabine Smolorz, Steffen Schubert, Steffen Emmert
The XPF/ERCC1 heterodimeric complex is essentially involved in nucleotide excision repair (NER), interstrand crosslink (ICL), and double-strand break repair. Defects in XPF lead to severe diseases like xeroderma pigmentosum (XP). Up until now, XP-F patient cells have been utilized for functional analyses. Due to the multiple roles of the XPF/ERCC1 complex, these patient cells retain at least one full-length allele and residual repair capabilities. Despite the essential function of the XPF/ERCC1 complex for the human organism, we successfully generated a viable immortalised human XPF knockout cell line with complete loss of XPF using the CRISPR/Cas9 technique in fetal lung fibroblasts (MRC5Vi cells)...
January 27, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28119062/baculovirus-based-genome-editing-in-primary-cells
#18
Maysam Mansouri, Zahra Ehsaei, Verdon Taylor, Philipp Berger
Genome editing in eukaryotes became easier in the last years with the development of nucleases that induce double strand breaks in DNA at user-defined sites. CRISPR/Cas9-based genome editing is currently one of the most powerful strategies. In the easiest case, a nuclease (e.g. Cas9) and a target defining guide RNA (gRNA) are transferred into a target cell. Non-homologous end joining (NHEJ) repair of the DNA break following Cas9 cleavage can lead to inactivation of the target gene. Specific repair or insertion of DNA with Homology Directed Repair (HDR) needs the simultaneous delivery of a repair template...
January 22, 2017: Plasmid
https://www.readbyqxmd.com/read/28118392/creation-of-novel-protein-variants-with-crispr-cas9-mediated-mutagenesis-turning-a-screening-by-product-into-a-discovery-tool
#19
Katherine F Donovan, Mudra Hegde, Meagan Sullender, Emma W Vaimberg, Cory M Johannessen, David E Root, John G Doench
CRISPR/Cas9 screening has proven to be a versatile tool for genomics research. Based on unexpected results from a genome-wide screen, we developed a CRISPR/Cas9-mediated approach to mutagenesis, exploiting the allelic diversity generated by error-prone non-homologous end-joining (NHEJ) to identify novel gain-of-function and drug resistant alleles of the MAPK signaling pathway genes MEK1 and BRAF. We define the parameters of a scalable technique to easily generate cell populations containing thousands of endogenous allelic variants to map gene functions...
2017: PloS One
https://www.readbyqxmd.com/read/28118114/coordination-of-the-ser2056-and-thr2609-clusters-of-dna-pkcs-in-regulating-gamma-rays-and-extremely-low-fluencies-of-alpha-particle-irradiation-to-g0-g1-phase-cells
#20
Hatsumi Nagasawa, Yu-Fen Lin, Takamitsu A Kato, John R Brogan, Hung-Ying Shih, Akihiro Kurimasa, Joel S Bedford, Benjamin P C Chen, John B Little
The catalytic subunit of DNA dependent protein kinase (DNA-PKcs) and its kinase activity are critical for mediation of non-homologous end-joining (NHEJ) of DNA double-strand breaks (DSB) in mammalian cells after gamma-ray irradiation. Additionally, DNA-PKcs phosphorylations at the T2609 cluster and the S2056 cluster also affect DSB repair and cellular sensitivity to gamma radiation. Previously we reported that phosphorylations within these two regions affect not only NHEJ but also homologous recombination repair (HRR) dependent DSB repair...
February 2017: Radiation Research
keyword
keyword
56274
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"