keyword
MENU ▼
Read by QxMD icon Read
search

Nonhomologous end joining

keyword
https://www.readbyqxmd.com/read/27924007/bridging-of-double-stranded-breaks-by-the-nonhomologous-end-joining-ligation-complex-is-modulated-by-dna-end-chemistry
#1
Dylan A Reid, Michael P Conlin, Yandong Yin, Howard H Chang, Go Watanabe, Michael R Lieber, Dale A Ramsden, Eli Rothenberg
The nonhomologous end-joining (NHEJ) pathway is the primary repair pathway for DNA double strand breaks (DSBs) in humans. Repair is mediated by a core complex of NHEJ factors that includes a ligase (DNA Ligase IV; L4) that relies on juxtaposition of 3' hydroxyl and 5' phosphate termini of the strand breaks for catalysis. However, chromosome breaks arising from biological sources often have different end chemistries, and how these different end chemistries impact the way in which the core complex directs the necessary transitions from end pairing to ligation is not known...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27924002/sfpq%C3%A2-nono-and-xlf-function-separately-and-together-to-promote-dna-double-strand-break-repair-via-canonical-nonhomologous-end-joining
#2
Lahcen Jaafar, Zhentian Li, Shuyi Li, William S Dynan
A complex of two related mammalian proteins, SFPQ and NONO, promotes DNA double-strand break repair via the canonical nonhomologous end joining (c-NHEJ) pathway. However, its mechanism of action is not fully understood. Here we describe an improved SFPQ•NONO-dependent in vitro end joining assay. We use this system to demonstrate that the SFPQ•NONO complex substitutes in vitro for the core c-NHEJ factor, XLF. Results are consistent with a model where SFPQ•NONO promotes sequence-independent pairing of DNA substrates, albeit in a way that differs in detail from XLF...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27922005/wrn-regulates-pathway-choice-between-classical-and-alternative-non-homologous-end-joining
#3
Raghavendra A Shamanna, Huiming Lu, Jessica K de Freitas, Jane Tian, Deborah L Croteau, Vilhelm A Bohr
Werner syndrome (WS) is an accelerated ageing disorder with genomic instability caused by WRN protein deficiency. Many features seen in WS can be explained by the diverse functions of WRN in DNA metabolism. However, the origin of the large genomic deletions and telomere fusions are not yet understood. Here, we report that WRN regulates the pathway choice between classical (c)- and alternative (alt)-nonhomologous end joining (NHEJ) during DNA double-strand break (DSB) repair. It promotes c-NHEJ via helicase and exonuclease activities and inhibits alt-NHEJ using non-enzymatic functions...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27911718/attacking-hiv-1-rna-versus-dna-by-sequence-specific-approaches-rnai-versus-crispr-cas
#4
REVIEW
Elena Herrera-Carrillo, Ben Berkhout
Human immunodeficiency virus type 1 (HIV-1) infection can be effectively controlled by potent antiviral drugs, but this never results in a cure. The patient should therefore take these drugs for the rest of his/her life, which can cause drug-resistance and adverse effects. Therefore, more durable therapeutic strategies should be considered, such as a stable gene therapy to protect the target T cells against HIV-1 infection. The development of potent therapeutic regimens based on the RNA interference (RNAi) and clustered regularly interspaced short palindromic repeats (CRISPR-Cas) mechanisms will be described, which can be delivered by lentiviral vectors...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27898094/crispr-cas9-aav-mediated-knock-in-at-nrl-locus-in-human-embryonic-stem-cells
#5
Xianglian Ge, Haitao Xi, Fayu Yang, Xiao Zhi, Yanghua Fu, Ding Chen, Ren-He Xu, Ge Lin, Jia Qu, Junzhao Zhao, Feng Gu
Clustered interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated genome engineering technologies are sparking a new revolution in biological research. This technology efficiently induces DNA double strand breaks at the targeted genomic sequence and results in indel mutations by the error-prone process of nonhomologous end joining DNA repair or homologous recombination with a DNA repair template. The efficiency of genome editing with CRISPR/Cas9 alone in human embryonic stem cells is still low...
November 29, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27895153/ubiquitylation-of-ku80-by-rnf126-promotes-completion-of-nhej-mediated-dna-repair
#6
Noriko Ishida, Tadashi Nakagawa, Shun-Ichiro Iemura, Akira Yasui, Hiroki Shima, Yasutake Katoh, Yuko Nagasawa, Toru Natsume, Kazuhiko Igarashi, Keiko Nakayama
Repair of damaged DNA is critical for maintenance of genetic information. In eukaryotes, DNA double-strand breaks (DSBs) are recognized by the Ku70-Ku80 heterodimer, which then recruits proteins that mediate repair by nonhomologous end-joining (NHEJ). Prolonged retention of Ku70/80 at DSBs prevents completion of repair, however, with ubiquitylation of Ku80 having been implicated in Ku70/80 dissociation from DNA. Here we identify RNF126 as a ubiquitin ligase that is recruited to DSBs and ubiquitylates Ku80, with UBE2D3 serving as an E2...
November 28, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27853172/lithium-promotes-dna-stability-and-survival-of-ischemic-retinal-neurocytes-by-upregulating-dna-ligase-iv
#7
Ying Yang, Nandan Wu, Sijia Tian, Fan Li, Huan Hu, Pei Chen, Xiaoxiao Cai, Lijun Xu, Jing Zhang, Zhao Chen, Jian Ge, Keming Yu, Jing Zhuang
Neurons display genomic fragility and show fragmented DNA in pathological degeneration. A failure to repair DNA breaks may result in cell death or apoptosis. Lithium protects retinal neurocytes following nutrient deprivation or partial nerve crush, but the underlying mechanisms are not well defined. Here we demonstrate that pretreatment with lithium protects retinal neurocytes from ischemia-induced damage and enhances light response in rat retina following ischemia-reperfusion injury. Moreover, we found that DNA nonhomologous end-joining (NHEJ) repair is implicated in this process because in ischemic retinal neurocytes, lithium significantly reduces the number of γ-H2AX foci (well-characterized markers of DNA double-strand breaks in situ) and increases the DNA ligase IV expression level...
November 17, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27849606/multiple-mechanisms-contribute-to-double-strand-break-repair-at-rereplication-forks-in-drosophila-follicle-cells
#8
Jessica L Alexander, Kelly Beagan, Terry L Orr-Weaver, Mitch McVey
Rereplication generates double-strand breaks (DSBs) at sites of fork collisions and causes genomic damage, including repeat instability and chromosomal aberrations. However, the primary mechanism used to repair rereplication DSBs varies across different experimental systems. In Drosophila follicle cells, developmentally regulated rereplication is used to amplify six genomic regions, two of which contain genes encoding eggshell proteins. We have exploited this system to test the roles of several DSB repair pathways during rereplication, using fork progression as a readout for DSB repair efficiency...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27798842/synthetic-lethality-between-paxx-and-xlf-in-mammalian-development
#9
Gabriel Balmus, Ana C Barros, Paul W G Wijnhoven, Chloé Lescale, Hélène Lenden Hasse, Katharina Boroviak, Carlos le Sage, Brendan Doe, Anneliese O Speak, Antonella Galli, Matt Jacobsen, Ludovic Deriano, David J Adams, Andrew N Blackford, Stephen P Jackson
PAXX was identified recently as a novel nonhomologous end-joining DNA repair factor in human cells. To characterize its physiological roles, we generated Paxx-deficient mice. Like Xlf(-/-) mice, Paxx(-/-) mice are viable, grow normally, and are fertile but show mild radiosensitivity. Strikingly, while Paxx loss is epistatic with Ku80, Lig4, and Atm deficiency, Paxx/Xlf double-knockout mice display embryonic lethality associated with genomic instability, cell death in the central nervous system, and an almost complete block in lymphogenesis, phenotypes that closely resemble those of Xrcc4(-/-) and Lig4(-/-) mice...
October 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27788957/targeting-phosphatidylinositol-4-kinase-iii%C3%AE-for-radiosensitization-a-potential-model-of-drug-repositioning-using-an-anti-hepatitis-c-viral-agent
#10
Jeanny Kwon, Dan Hyo Kim, Ji Min Park, Young Hee Park, Yeo Hyun Hwang, Hong-Gyun Wu, Kyung Hwan Shin, In Ah Kim
PURPOSE: To investigate which isotype of phosphatidylinositol 4-kinase (PI4K) may affect radiosensitivity and examine whether anti-hepatitis C viral (HCV) agents, some of which have been shown to inhibit PI4K IIIα activity, could be repositioned as a radiosensitizer in human cancer cells. METHODS AND MATERIALS: U251, BT474, and HepG2 cell lines and normal human astrocyte were used. Ribonucleic acid interference, clonogenic assays, Western blotting, immunofluorescence, annexin V assay, lysotracker staining, and β-galactosidase assay were performed...
November 15, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27780671/detailed-analysis-of-targeted-gene-mutations-caused-by-the-platinum-fungal-talens-in-aspergillus-oryzae-rib40-strain-and-a-ligd-disruptant
#11
Osamu Mizutani, Takayuki Arazoe, Kenji Toshida, Risa Hayashi, Shuichi Ohsato, Tetsushi Sakuma, Takashi Yamamoto, Shigeru Kuwata, Osamu Yamada
Transcription activator-like effector nucleases (TALENs), which can generate DNA double-strand breaks at specific sites in the desired genome locus, have been used in many organisms as a tool for genome editing. In Aspergilli, including Aspergillus oryzae, however, the use of TALENs has not been validated. In this study, we performed genome editing of A. oryzae wild-type strain via error of nonhomologous end-joining (NHEJ) repair by transient expression of high-efficiency Platinum-Fungal TALENs (PtFg TALENs)...
October 22, 2016: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/27757426/tie2-mediated-tyrosine-phosphorylation-of-h4-regulates-dna-damage-response-by-recruiting-abl1
#12
Mohammad B Hossain, Rehnuma Shifat, David G Johnson, Mark T Bedford, Konrad R Gabrusiewicz, Nahir Cortes-Santiago, Xuemei Luo, Zhimin Lu, Ravesanker Ezhilarasan, Erik P Sulman, Hong Jiang, Shawn S C Li, Frederick F Lang, Jessica Tyler, Mien-Chie Hung, Juan Fueyo, Candelaria Gomez-Manzano
DNA repair pathways enable cancer cells to survive DNA damage induced after genotoxic therapies. Tyrosine kinase receptors (TKRs) have been reported as regulators of the DNA repair machinery. TIE2 is a TKR overexpressed in human gliomas at levels that correlate with the degree of increasing malignancy. Following ionizing radiation, TIE2 translocates to the nucleus, conferring cells with an enhanced nonhomologous end-joining mechanism of DNA repair that results in a radioresistant phenotype. Nuclear TIE2 binds to key components of DNA repair and phosphorylates H4 at tyrosine 51, which, in turn, is recognized by the proto-oncogene ABL1, indicating a role for nuclear TIE2 as a sensor for genotoxic stress by action as a histone modifier...
April 2016: Science Advances
https://www.readbyqxmd.com/read/27746407/cloning-localization-and-focus-formation-at-dna-damage-sites-of-canine-xlf
#13
Manabu Koike, Yasutomo Yutoku, Aki Koike
Understanding the molecular mechanisms of DNA double-strand break (DSB) repair processes, especially nonhomologous DNA-end joining (NHEJ), is critical for developing next-generation radiotherapies and chemotherapeutics for human and animal cancers. The localization, protein-protein interactions and post-translational modifications of core NHEJ factors, such as human Ku70 and Ku80, might play critical roles in controlling NHEJ activity. XRCC4-like factor (XLF) is a core NHEJ factor and plays a key role in the Ku-dependent NHEJ repair process in human cells...
October 14, 2016: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/27732795/a-life-investigating-pathways-that-repair-broken-chromosomes
#14
James E Haber
Double-strand breaks (DSBs) pose a severe challenge to genome integrity; consequently, cells have developed efficient mechanisms to repair DSBs through several pathways of homologous recombination and other nonhomologous end-joining processes. Much of our understanding of these pathways has come from the analysis of site-specific DSBs created by the HO endonuclease in the budding yeast Saccharomyces cerevisiae. I was fortunate to get in on the ground floor of analyzing the fate of synchronously induced DSBs through the study of what I coined "in vivo biochemistry...
November 23, 2016: Annual Review of Genetics
https://www.readbyqxmd.com/read/27721405/eaf2-regulates-dna-repair-through-ku70-ku80-in-the-prostate
#15
J Ai, L E Pascal, L Wei, Y Zang, Y Zhou, X Yu, Y Gong, S Nakajima, J B Nelson, A S Levine, L Lan, Z Wang
Androgens are known to protect prostate cancer cells from DNA damage. Recent studies showed regulation of DNA repair genes by androgen receptor signaling in prostate cancers. ELL-associated factor 2 (EAF2) is an androgen-regulated tumor suppressor and its intracellular localization can be modulated by ultraviolet light, suggesting a potential role for EAF2 in androgen regulation of DNA repair in prostate cancer cells. Here we show that knockdown of EAF2 or its homolog EAF1 sensitized prostate cancer cells to DNA damage and the sensitization did not require p53...
October 10, 2016: Oncogene
https://www.readbyqxmd.com/read/27703001/different-dna-end-configurations-dictate-which-nhej-components-are-most-important-for-joining-efficiency
#16
Howard H Y Chang, Go Watanabe, Christina A Gerodimos, Takashi Ochi, Tom L Blundell, Stephen P Jackson, Michael R Lieber
The nonhomologous DNA end-joining (NHEJ) pathway is a key mechanism for repairing dsDNA breaks that occur often in eukaryotic cells. In the simplest model, these breaks are first recognized by Ku, which then interacts with other NHEJ proteins to improve their affinity at DNA ends. These include DNA-PKcs and Artemis for trimming the DNA ends; DNA polymerase μ and λ to add nucleotides; and the DNA ligase IV complex to ligate the ends with the additional factors, XRCC4 (X-ray repair cross-complementing protein 4), XLF (XRCC4-like factor/Cernunos), and PAXX (paralog of XRCC4 and XLF)...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27701148/inhibition-of-cdk4-6-protects-against-radiation-induced-intestinal-injury-in-mice
#17
Liang Wei, Brian J Leibowitz, Xinwei Wang, Michael Epperly, Joel Greenberger, Lin Zhang, Jian Yu
Radiotherapy causes dose-limiting toxicity and long-term complications in rapidly renewing tissues, including the gastrointestinal tract. Currently, there is no FDA-approved agent for the prevention or treatment of radiation-induced intestinal injury. In this study, we have shown that PD 0332991 (PD), an FDA-approved selective inhibitor of cyclin-dependent kinase 4/6 (CDK4/6), prevents radiation-induced lethal intestinal injury in mice. Treating mice with PD or a structurally distinct CDK4/6 inhibitor prior to radiation blocked proliferation and crypt apoptosis and improved crypt regeneration...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27688775/high-fidelity-reprogrammed-human-ipscs-have-a-high-efficacy-of-dna-repair-and-resemble-hescs-in-their-myc-transcriptional-signature
#18
Pratik K Nagaria, Carine Robert, Tea Soon Park, Jeffrey S Huo, Elias T Zambidis, Feyruz V Rassool
Human induced pluripotent stem cells (hiPSCs) are reprogrammed from adult or progenitor somatic cells and must make substantial adaptations to ensure genomic stability in order to become "embryonic stem cell- (ESC-) like." The DNA damage response (DDR) is critical for maintenance of such genomic integrity. Herein, we determined whether cell of origin and reprogramming method influence the DDR of hiPSCs. We demonstrate that hiPSCs derived from cord blood (CB) myeloid progenitors (i.e., CB-iPSC) via an efficient high-fidelity stromal-activated (sa) method closely resembled hESCs in DNA repair gene expression signature and irradiation-induced DDR, relative to hiPSCs generated from CB or fibroblasts via standard methods...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27675958/rnf8-regulates-nonhomologous-end-joining-and-dna-pk-recruitment-to-dna-double-strand-break-sites
#19
S Gao, Y Surovtseva, R S Bindra
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27671945/selection-of-error-less-synthetic-genes-in-yeast
#20
Hisashi Hoshida, Tohru Yarimizu, Rinji Akada
Conventional gene synthesis is usually accompanied by sequence errors, which are often deletions derived from chemically synthesized oligonucleotides. Such deletions lead to frame shifts and mostly result in premature translational terminations. Therefore, in-frame fusion of a marker gene to the downstream of a synthetic gene is an effective strategy to select for frame-shift-free synthetic genes. Functional expression of fused marker genes indicates that synthetic genes are translated without premature termination, i...
2017: Methods in Molecular Biology
keyword
keyword
7539
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"