keyword
MENU ▼
Read by QxMD icon Read
search

"Genomic integration"

keyword
https://www.readbyqxmd.com/read/28335006/a-platform-for-functional-assessment-of-large-variant-libraries-in-mammalian-cells
#1
Kenneth A Matreyek, Jason J Stephany, Douglas M Fowler
Sequencing-based, massively parallel genetic assays have revolutionized our ability to quantify the relationship between many genotypes and a phenotype of interest. Unfortunately, variant library expression platforms in mammalian cells are far from ideal, hindering the study of human gene variants in their physiologically relevant cellular contexts. Here, we describe a platform for phenotyping variant libraries in transfectable mammalian cell lines in two steps. First, a landing pad cell line with a genomically integrated, Tet-inducible cassette containing a Bxb1 recombination site is created...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334850/aicardi-gouti%C3%A3-res-syndrome-protein-trex1-suppresses-l1-and-maintains-genome-integrity-through-exonuclease-independent-orf1p-depletion
#2
Peng Li, Juan Du, John L Goodier, Jingwei Hou, Jian Kang, Haig H Kazazian, Ke Zhao, Xiao-Fang Yu
Maintaining genome integrity is important for cells and damaged DNA triggers autoimmunity. Previous studies have reported that Three-prime repair exonuclease 1(TREX1), an endogenous DNA exonuclease, prevents immune activation by depleting damaged DNA, thus preventing the development of certain autoimmune diseases. Consistently, mutations in TREX1 are linked with autoimmune diseases such as systemic lupus erythematosus, Aicardi-Goutières syndrome (AGS) and familial chilblain lupus. However, TREX1 mutants competent for DNA exonuclease activity are also linked to AGS...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334827/yeast-hrq1-shares-structural-and-functional-homology-with-the-disease-linked-human-recq4-helicase
#3
Cody M Rogers, Joseph Che-Yen Wang, Hiroki Noguchi, Tsuyoshi Imasaki, Yuichiro Takagi, Matthew L Bochman
The five human RecQ helicases participate in multiple processes required to maintain genome integrity. Of these, the disease-linked RecQ4 is the least studied because it poses many technical challenges. We previously demonstrated that the yeast Hrq1 helicase displays similar functions to RecQ4 in vivo, and here, we report the biochemical and structural characterization of these enzymes. In vitro, Hrq1 and RecQ4 are DNA-stimulated ATPases and robust helicases. Further, these activities were sensitive to DNA sequence and structure, with the helicases preferentially unwinding D-loops...
February 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334334/p53-and-its-mutants-on-the-slippery-road-from-stemness-to-carcinogenesis
#4
Alina Molchadsky, Varda Rotter
Normal development, tissue homeostasis and regeneration following injury rely on the proper functions of wide repertoire of stem cells (SCs) persisting during embryonic period and throughout the adult life. Therefore, SCs employ robust mechanisms to preserve their genomic integrity and avoid heritage of mutations to their daughter cells. Importantly, propagation of SCs with faulty DNA as well as dedifferentiation of genomically altered somatic cells may result in derivation of cancer SCs, which are considered to be the driving force of the tumorigenic process...
March 15, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28329681/sirt6-promotes-dna-end-joining-in-ipscs-derived-from-old-mice
#5
Wen Chen, Nana Liu, Hongxia Zhang, Haiping Zhang, Jing Qiao, Wenwen Jia, Songcheng Zhu, Zhiyong Mao, Jiuhong Kang
Induced pluripotent stem cells (iPSCs) have great potential for treating age-related diseases, but the genome integrity of iPSCs is critically important. Here, we demonstrate that non-homologous end joining (NHEJ), rather than homologous recombination (HR), is less efficient in iPSCs from old mice than young mice. We further find that Sirt6 is downregulated in iPSCs from old mice. Sirt6 directly binds to Ku80 and facilitates the Ku80/DNA-PKcs interaction, thus promoting DNA-PKcs phosphorylation at residue S2056, leading to efficient NHEJ...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28327192/dna-double-strand-breaks-in-human-induced-pluripotent-stem-cell-reprogramming-and-long-term-in-vitro-culturing
#6
Pavel Simara, Lenka Tesarova, Daniela Rehakova, Pavel Matula, Stanislav Stejskal, Ales Hampl, Irena Koutna
BACKGROUND: Human induced pluripotent stem cells (hiPSCs) play roles in both disease modelling and regenerative medicine. It is critical that the genomic integrity of the cells remains intact and that the DNA repair systems are fully functional. In this article, we focused on the detection of DNA double-strand breaks (DSBs) by phosphorylated histone H2AX (known as γH2AX) and p53-binding protein 1 (53BP1) in three distinct lines of hiPSCs, their source cells, and one line of human embryonic stem cells (hESCs)...
March 21, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28327001/autophagy-promotes-the-repair-of-radiation-induced-dna-damage-in-bone-marrow-hematopoietic-cells-via-enhanced-stat3-signaling
#7
Fei Xu, Xin Li, Lili Yan, Na Yuan, Yixuan Fang, Yan Cao, Li Xu, Xiaoying Zhang, Lan Xu, Chaorong Ge, Ni An, Gaoyue Jiang, Jialing Xie, Han Zhang, Jiayi Jiang, Xiaotian Li, Lei Yao, Suping Zhang, Daohong Zhou, Jianrong Wang
Autophagy protects hematopoietic cells from radiation damage in part by promoting DNA damage repair. However, the molecular mechanisms by which autophagy regulates DNA damage repair remain largely elusive. Here, we report that this radioprotective effect of autophagy depends on STAT3 signaling in murine bone marrow mononuclear cells (BM-MNCs). Specifically, we found that STAT3 activation and nuclear translocation in BM-MNCs were increased by activation of autophagy with an mTOR inhibitor and decreased by knockout of the autophagy gene Atg7...
March 2017: Radiation Research
https://www.readbyqxmd.com/read/28325772/tet3-mediated-dna-oxidation-promotes-atr-dependent-dna-damage-response
#8
Dewei Jiang, Shu Wei, Fei Chen, Ying Zhang, Jiali Li
An efficient, accurate, and timely DNA damage response (DDR) is crucial for the maintenance of genome integrity. Here, we report that ten-eleven translocation dioxygenase (TET) 3-mediated conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in response to ATR-dependent DDR regulates DNA repair. ATR-dependent DDR leads to dynamic changes in 5hmC levels and TET3 enzymatic activity. We show that TET3 is an ATR kinase target that oxidizes DNA during ATR-dependent DNA damage repair. Modulation of TET3 expression and activity affects DNA damage signaling and DNA repair and consequently cell death...
March 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28325498/the-role-of-rnase-h2-in-processing-ribonucleotides-incorporated-during-dna-replication
#9
Jessica S Williams, Daniel B Gehle, Thomas A Kunkel
Saccharomyces cerevisiae RNase H2 resolves RNA-DNA hybrids formed during transcription and it incises DNA at single ribonucleotides incorporated during nuclear DNA replication. To distinguish between the roles of these two activities in maintenance of genome stability, here we investigate the phenotypes of a mutant of yeast RNase H2 (rnh201-RED; ribonucleotide excision defective) that retains activity on RNA-DNA hybrids but is unable to cleave single ribonucleotides that are stably incorporated into the genome...
March 6, 2017: DNA Repair
https://www.readbyqxmd.com/read/28325279/gene-is-time-efficient-and-accurate-analysis-of-viral-integration-events-in-large-scale-gene-therapy-data
#10
Saira Afzal, Stefan Wilkening, Christof von Kalle, Manfred Schmidt, Raffaele Fronza
Integration site profiling and clonality analysis of viral vector distribution in gene therapy is a key factor to monitor the fate of gene-corrected cells, assess the risk of malignant transformation, and establish vector biosafety. We developed the Genome Integration Site Analysis Pipeline (GENE-IS) for highly time-efficient and accurate detection of next-generation sequencing (NGS)-based viral vector integration sites (ISs) in gene therapy data. It is the first available tool with dual analysis mode that allows IS analysis both in data generated by PCR-based methods, such as linear amplification method PCR (LAM-PCR), and by rapidly evolving targeted sequencing (e...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28325102/building-up-and-breaking-down-mechanisms-controlling-recombination-during-replication
#11
Dana Branzei, Barnabas Szakal
The complete and faithful duplication of the genome is an essential prerequisite for proliferating cells to maintain genome integrity. This objective is greatly challenged by DNA damage encountered during replication, which causes fork stalling and in certain cases, fork breakage. DNA damage tolerance (DDT) pathways mitigate the effects on fork stability induced by replication fork stalling by mediating damage-bypass and replication fork restart. These DDT mechanisms, largely relying on homologous recombination (HR) and specialized polymerases, can however contribute to genome rearrangements and mutagenesis...
March 22, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28322935/early-pathogenesis-during-infectious-bursal-disease-in-susceptible-chickens-is-associated-with-changes-in-b-cell-genomic-methylation-and-loss-of-genome-integrity
#12
Nick A Ciccone, Lorraine P Smith, William Mwangi, Amy Boyd, Andrew J Broadbent, Adrian L Smith, Venugopal Nair
We propose a model by which an increase in the genomic modification, 5-hydroxymethylcytosine (5hmC), contributes to B cell death within the chicken bursa of Fabricus (BF) infected with infectious bursal disease virus (IBDV). Our findings indicate that, following an IBDV infection, Rhode Island Red (RIR) chickens have fewer surviving B cells and higher levels of 5hmC in the BF than the more resistant 15l line of birds. Elevated genomic 5hmC levels within the RIR BF are associated with markers of immune responses: infiltrating T cells and increased expression of CD40L, FasL and iNOS...
March 17, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28320736/arabidopsis-retinoblastoma-related-directly-regulates-dna-damage-responses-through-functions-beyond-cell-cycle-control
#13
Beatrix M Horvath, Hana Kourova, Szilvia Nagy, Edit Nemeth, Zoltan Magyar, Csaba Papdi, Zaki Ahmad, Gabino F Sanchez-Perez, Serena Perilli, Ikram Blilou, Aladár Pettkó-Szandtner, Zsuzsanna Darula, Tamas Meszaros, Pavla Binarova, Laszlo Bogre, Ben Scheres
The rapidly proliferating cells in plant meristems must be protected from genome damage. Here, we show that the regulatory role of the Arabidopsis RETINOBLASTOMA RELATED (RBR) in cell proliferation can be separated from a novel function in safeguarding genome integrity. Upon DNA damage, RBR and its binding partner E2FA are recruited to heterochromatic γH2AX-labelled DNA damage foci in an ATM- and ATR-dependent manner. These γH2AX-labelled DNA lesions are more dispersedly occupied by the conserved repair protein, AtBRCA1, which can also co-localise with RBR foci...
March 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28315825/effects-of-florida-red-tides-on-histone-variant-expression-and-dna-methylation-in-the-eastern-oyster-crassostrea-virginica
#14
Rodrigo Gonzalez-Romero, Victoria Suarez-Ulloa, Javier Rodriguez-Casariego, Daniel Garcia-Souto, Gabriel Diaz, Abraham Smith, Juan Jose Pasantes, Gary Rand, Jose M Eirin-Lopez
Massive algal proliferations known as Harmful Algal Blooms (HABs) represent one of the most important threats to coastal areas. Among them, the so-called Florida Red Tides (FRTs, caused by blooms of the dinoflagellate Karenia brevis and associated brevetoxins) are particularly detrimental in the southeastern U.S., causing high mortality rates and annual losses in excess of $40 million. The ability of marine organisms to cope with environmental stressors (including those produced during HABs) is influenced by genetic and epigenetic mechanisms, the latter resulting in phenotypic changes caused by heritable modifications in gene expression, without involving changes in the genetic (DNA) sequence...
March 7, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28314779/an-atr-dependent-function-for-the-ddx19-rna-helicase-in-nuclear-r-loop-metabolism
#15
Dana Hodroj, Bénédicte Recolin, Kamar Serhal, Susan Martinez, Nikolay Tsanov, Raghida Abou Merhi, Domenico Maiorano
Coordination between transcription and replication is crucial in the maintenance of genome integrity. Disturbance of these processes leads to accumulation of aberrant DNA:RNA hybrids (R-loops) that, if unresolved, generate DNA damage and genomic instability. Here we report a novel, unexpected role for the nucleopore-associated mRNA export factor Ddx19 in removing nuclear R-loops formed upon replication stress or DNA damage. We show, in live cells, that Ddx19 transiently relocalizes from the nucleopore to the nucleus upon DNA damage, in an ATR/Chk1-dependent manner, and that Ddx19 nuclear relocalization is required to clear R-loops...
March 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28314775/insights-into-rad3-kinase-recruitment-from-the-crystal-structure-of-the-dna-damage-checkpoint-protein-rad26
#16
Kasper Røjkjær Andersen
Metabolic products and environmental factors constantly damage DNA. To protect against these insults and maintain genome integrity, cells have evolved mechanisms to repair DNA lesions. One such mechanism involves Rad3, a master kinase coordinating the DNA damage response. Rad26 is a functional subunit of the Rad3-Rad26 complex and responsible for bringing the kinase to sites of DNA damage. Here, I present the crystal structure of Rad26 and identify the elements important for recruiting Rad3. The structure suggests that Rad26 is a dimer with a conserved interface in the N-terminal part of the protein...
March 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28306242/excision-repair-initiated-enzyme-assisted-bicyclic-cascade-signal-amplification-for-ultrasensitive-detection-of-uracil-dna-glycosylase
#17
Li-Juan Wang, Ming Ren, Qianyi Zhang, Bo Tang, Chun-Yang Zhang
Uracil-DNA glycosylase (UDG) is an important base excision repair (BER) enzyme responsible for the repair of uracil-induced DNA lesion and the maintenance of genomic integrity, while the aberrant expression of UDG is associated with a variety of cancers. Thus the accurate detection of UDG activity is essential to biomedical research and clinical diagnosis. Here, we develop a fluorescent method for ultrasensitive detection of UDG activity using excision repair-initiated enzyme-assisted bicyclic cascade signal amplification...
March 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28301767/progress-in-human-and-tetrahymena-telomerase-structure
#18
Henry Chan, Yaqiang Wang, Juli Feigon
Telomerase is an RNA-protein complex that extends the 3' ends of linear chromosomes, using a unique telomerase reverse transcriptase (TERT) and template in the telomerase RNA (TR), thereby helping to maintain genome integrity. TR assembles with TERT and species-specific proteins, and telomerase function in vivo requires interaction with telomere-associated proteins. Over the past two decades, structures of domains of TR and TERT as well as other telomerase- and telomere-interacting proteins have provided insights into telomerase function...
March 15, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28299675/a-regulatory-role-for-runx1-runx3-in-the-maintenance-of-genomic-integrity
#19
Vaidehi Krishnan, Yoshiaki Ito
All human cells are constantly attacked by endogenous and exogenous agents that damage the integrity of their genomes. Yet, the ensuing damage is mostly fixed and very rarely gives rise to genomic defects that promote cancer formation. This is due to the co-ordinated functioning of DNA repair proteins and checkpoint mechanisms that accurately detect and repair DNA damage to ensure genomic fitness. According to accumulating evidence, the RUNX family of transcription factors participate in the maintenance of genomic stability through transcriptional and non-transcriptional mechanisms...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28295042/generation-of-non-viral-transgene-free-hepatocyte-like-cells-with-piggybac-transposon
#20
Hokahiro Katayama, Kentaro Yasuchika, Yuya Miyauchi, Hidenobu Kojima, Ryoya Yamaoka, Takayuki Kawai, Elena Yukie Yoshitoshi, Satoshi Ogiso, Sadahiko Kita, Katsutaro Yasuda, Naoya Sasaki, Ken Fukumitsu, Junji Komori, Takamichi Ishii, Shinji Uemoto
Somatic cells can be reprogrammed to induced hepatocyte-like cells (iHeps) by overexpressing certain defined factors in direct reprogramming techniques. Of the various methods to deliver genes into cells, typically used genome-integrating viral vectors are associated with integration-related adverse events such as mutagenesis, whereas non-integrating viral vectors have low efficiency, making viral vectors unsuitable for clinical application. Therefore, we focused on developing a transposon system to establish a non-viral reprogramming method...
March 15, 2017: Scientific Reports
keyword
keyword
59400
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"