ProteinsGenesProteinLesionsMutationsGeneticEfferent visual pathwayEnzymesMetabolic pathwaysLagging-strandPolymerase theta-mediatedDamage inducedHomology DirectEnzymatic pathwayIntracellularFanconiCellularMechanismsCytosolicMethylationEnzymeStrandsSynthesis pathwaySubunitTMEJKinaseMechanismRegulationNHEJRecombinationIncluding DNA double-strandHypoxiaSingle-strandedInflammatoryChromosomeHelicaseCRISPR-Cas9OrganismProgressionModulationTherapiesTherapeuticGene expressionVitroLigaseDouble-strand breaksOccursViralSTINGAutophagyFunctionallyGenomicConvertsCellsSequenceTranscription

Proteins11

• Epirubicin was reported to block DNA replication either through direct DNA damage or indirectly through inhibition of replication proteins such as topoisomerase. (nature.com)
• A complex network of interacting proteins and enzymes is required for DNA replication. (kegg.jp)
• Candidate genes for testing in the RNAi screen were curated from quantitative proteomic screens, IFN-beta and ISD stimulated mRNA expression profiles, and a selection of domain-based proteins including helicases, cytoplasmically located DNA- binding proteins and a set of potential negative regulators including phosphatases, deubiquitinases and known signaling proteins. (harvard.edu)
• The solution structure of the amino-terminal domain of human DNA polymerase epsilon subunit B is homologous to C-domains of AAA+ proteins. (nih.gov)
• The mammalian mitochondrial proteome is under dual genomic control, with 99% of proteins encoded by the nuclear genome and 13 originating from the mitochondrial DNA (mtDNA). (nih.gov)
• For instance, DSBs are repaired by DSB repair proteins, while improperly paired DNA bases are repaired by mismatch repair proteins. (globalhealthnewswire.com)
• Director Myung said, "This research has revealed a new function of the mismatch repair protein MSH2-MSH3 in regulating DSB repair," adding, "The repair proteins that have been believed so far to act independently in the mismatch repair, double-stranded break repair, and TMEJ repair pathways are now shown to closely interact each other for proper maintenance of genomic integrity. (globalhealthnewswire.com)
• Scientists could potentially tweak proteins involved in the pathway to preferentially steer the outcome toward replacement with DNA, which is important for gene therapy for hereditary diseases. (sciencedaily.com)
• In contrast, nonpathogenic SIVagm infection induced DNA methylation in genes coding for regulatory proteins such as LAG-3, arginase-2, interleukin-21 and interleukin-31. (biomedcentral.com)
• This report examines various microarray platforms and the technologies that are utilized to detect DNA and proteins for the purpose of drug discovery, disease diagnosis and disease monitoring. (bccresearch.com)
• DNA-PKcs is modified by phosphorylation and has been shown to interact with Ku70/Ku80, KIP, DNA-ligase IV, and XRCC4 proteins. (biolegend.com)

Genes12

• The cGAS-STING pathway is a component of the innate immune system that functions to detect the presence of cytosolic DNA and, in response, trigger expression of inflammatory genes that can lead to senescence or to the activation of defense mechanisms. (wikipedia.org)
• The presence of DNA in the cytosol is indicative of cellular damage or infection and leads to activation of genes associated with the immune response. (wikipedia.org)
• We set out to identify novel components of the ISD pathway by developing a large-scale loss-of-function genetic perturbation screen of 1003 candidate genes. (harvard.edu)
• In addition to the identification of novel ISD pathway components, our enriched screening data set may provide a useful resource of candidate genes involved in the response to cytosolic DNA. (harvard.edu)
• We are honored to collaborate with the country's leading cancer experts to help advance the understanding of cancer risk, the genes associated with it, and take steps to end preventable hereditary cancers," David Becker, CSO of Pathway Genomics, said in a statement. (genomeweb.com)
• The PROMPT team welcomes Pathway Genomics to the group seeking to improve our understanding of mutations in genes other than BRCA1 and BRCA2," Mark Robson, co-founder of PROMPT and director of clinical genetics service at Memorial Sloan-Kettering, said. (genomeweb.com)
• Furthermore, extended hypoxia can lead to long-term persistent silencing of certain DNA repair genes, including BRCA1 and MLH1, revealing a mechanism by which tumor suppressor genes can be inactivated. (bibbase.org)
• To find out which DNA repair enzymes are critical to homology-directed repair after CRISPR cutting, Richardson and Corn employed a technique called CRISPR interference (CRISPRi) to knock out, one at a time, more than 2,000 genes known or suspected to be involved in DNA repair, a function critical to a healthy cell. (sciencedaily.com)
• Between 15 and 18% of genes with DNA methylation changes were differentially expressed in CD4 + T cells in vivo. (biomedcentral.com)
• Instead of activating DNA repair, the altered ATM protein allows variants to accumulate in other genes, which may cause cells to grow and divide in an uncontrolled way. (medlineplus.gov)
• In each category, studies related to growth control genes, cell proliferation, apoptosis, DNA repair genes, antioxidant and drug detoxification genes, genes of drug metabolizing enzymes, tissue remodeling genes and genes of antibody-dependent cellular cytotoxicity were discussed separately. (researchsquare.com)
• The goal of our search was to identify publications describing the role of specific genes, gene signatures, or molecular pathways and their effects in response to environmental exposures. (cdc.gov)

Protein20

• Upon binding DNA, the protein cyclic GMP-AMP Synthase (cGAS) triggers reaction of GTP and ATP to form cyclic GMP-AMP (cGAMP). (wikipedia.org)
• identified cGAS as the DNA-sensing protein able to trigger interferon beta by synthesizing the second messenger, 2'3'-cGAMP. (wikipedia.org)
• Moreover, even after entering the HDR pathway, an unclear mechanism involving protein 53BP1 and Shieldin complex blocks the pathway from progressing. (europa.eu)
• Proliferative control in cancer cells is frequently disrupted by mutations in the retinoblastoma protein (RB) pathway. (bepress.com)
• RB1 deletion in retinoblastoma protein pathway-disrupted cells results in DNA damage and cancer progression" Molecular and Cellular Biology Vol. 39 Iss. (bepress.com)
• Yin and Steitz, 2002 ), implying that DNAP-I follows a complex enzymatic pathway that contains numerous intermediates, many of which have not yet been observed in protein crystals. (elifesciences.org)
• We interrogated multiple human and murine primary and immortalized cells, tested several Type-I IFN reporters, and considered multiple loss-of-function strategies before proceeding with an RNAi screen whereby mouse embryonic fibroblasts were stimulated with ISD and Type-IFN pathway activation was assessed by measuring Cxcl10 protein by ELISA. (harvard.edu)
• Additionally, we evaluated protein-protein interactions of our strongest validated hits to develop a network model of the ISD pathway. (harvard.edu)
• Methyl groups are important for numerous cellular functions such as DNA methylation, phosphatidylcholine synthesis, and protein synthesis. (nih.gov)
• Laser microirradiation is used to mimic the DSBs in cells and measure the recruitment of green flurecent protein-labeled MSH2 (GFP-MSH2) or EXO1 (GFP-EXO1) to the DNA damage site (indicated by the red line) under a confocal microscope. (globalhealthnewswire.com)
• Specifically, it was revealed that MSH2-MSH3, a DNA mismatch repair protein, actually plays a crucial role in the DSB repair process. (globalhealthnewswire.com)
• This event also causes phosphorylation of the Fanconi anemia (FA) protein FANCI, triggering its monoubiquitination of the key DNA repair factor FANCD2 by the FA core E3 ligase complex, thereby promoting this central pathway of DNA repair which permits replication to be restarted. (elsevierpure.com)
• On the other hand, RNA is a single chain of nucleotides primarily involved in protein synthesis following the master plan outlined by DNA. (aboutdarwin.com)
• Additionally, the ATM protein assists cells in recognizing damaged or broken DNA strands. (medlineplus.gov)
• The ATM protein coordinates DNA repair by activating enzymes that fix the broken strands. (medlineplus.gov)
• Because of its central role in cell division and DNA repair, the ATM protein is of great interest in cancer research. (medlineplus.gov)
• Cells without any functional ATM protein are hypersensitive to radiation and do not respond normally to DNA damage. (medlineplus.gov)
• These microarrays, which include DNA microarrays, protein microarrays, tissue microarrays, low complexity microarrays and carbohydrate microarrays, are excellent tools for gene expression profiling, biomarker profiling and diagnostics. (bccresearch.com)
• A model where resection-dependent and independent pathways are entirely separated can only reproduce experimental repair kinetics with additional restraints on end motion and protein recruitment. (bvsalud.org)
• DNA-protein kinase catalytic subunit (DNA-PKcs) also known as DNA-activated kinase is a nuclear 460-470 kD serine threonine kinase involved in double-stranded DNA break repair, VDJ recombination, and transcriptional modulation. (biolegend.com)

Lesions6

• The current study aimed to advance our understanding of tirapazamine-induced lesions and the pathways involved in their repair. (aacrjournals.org)
• Such outcomes can result from both the repair and misrepair of DNA ends, which arise from a variety of lesions including DNA double strand breaks (DSBs), collapsed replication forks and dysfunctional telomeres. (ox.ac.uk)
• Here we review the mechanisms by which non-homologous end joining (NHEJ) and homologous recombination (HR) repair pathways can both promote chromosomal rearrangements and also suppress them in response to such lesions, in accordance with their increasingly recognised tumour suppressor function. (ox.ac.uk)
• Some individuals with MS and other CNS inflammatory syndromes also may experience homonymous visual field defects caused by lesions in retrochiasmal or retrogeniculate (posterior) regions of the afferent visual pathway. (medscape.com)
• Efferent visual pathway lesions can create a perception of oscillopsia, a visual disturbance in which objects appear to jiggle or move owing to nystagmus (involuntary eye movements). (medscape.com)
• Optic neuritis refers to an inflammatory injury of the optic nerve and represents a common afferent visual pathway manifestation of MS. Less often, homonymous visual field defects caused by retrogeniculate lesions are encountered. (medscape.com)

Mutations12

• Mutations in the positively charged residues completely abrogate DNA binding and subsequent interferon production through STING. (wikipedia.org)
• Intriguingly, RB1 mutations can arise late in tumorigenesis in cancer cells whose RB pathway is already compromised by another mutation. (bepress.com)
• In this study, we present evidence for increased DNA damage and instability in cancer cells with RB pathway defects when RB1 mutations are induced. (bepress.com)
• The pathway - which has been found to be upregulated in many patients with hereditary breast cancer, ovarian cancer, and prostate cancer, specifically those involving BRCA1 and BRCA2 mutations - has been laid out step by step in a published article in Nature, and the new knowledge could lead to new therapies for cancer. (anxiety-stress-management.com)
• People with these breast cancer mutations, their cancers rely on polymerase theta's repair pathway to keep the tumors alive and repair DNA damage in the cancerous tissue," said Stroik, a postdoctoral researcher in Ramsden's lab. (anxiety-stress-management.com)
• Mutations/polymorphisms in the 55 kDa subunit of DNA polymerase epsilon in human colorectal cancer. (nih.gov)
• DNA alkylating is the transfer of alkyl groups to particular bases, resulting in alkylation products such as O2‐alkylthymine and O6‐methylguanine that lead to DNA mutations. (apexbt.com)
• NEW YORK (GenomeWeb) - Genetic testing laboratory Pathway Genomics today announced a partnership with the Prospective Registry of Multiplex Testing, an online registry for patients who have undergone testing for cancer-causing genetic mutations. (genomeweb.com)
• These are considered the most severe type of DNA damage, capable of causing genetic mutations or cell death. (globalhealthnewswire.com)
• On the other hand, DNA repaired by polymerase theta-mediated end-joining (TMEJ) can result in the loss of some genetic information and cause mutations. (globalhealthnewswire.com)
• After the long-range resection, the damaged DNA is repaired through error-free HR. Furthermore, it was discovered that the binding of MSH2-MSH3 inhibits the access of POLθ, which mediates a more error-prone TMEJ pathway, thereby preventing mutations that may occur during DSB repair. (globalhealthnewswire.com)
• Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. (lu.se)

Genetic5

• Briefly put, both DNA (Deoxyribonucleic Acid) and RNA (Ribonucleic Acid) carry genetic information of all life forms guiding their biological functions. (aboutdarwin.com)
• DNA, a double-stranded molecule, is the primary genetic material directly responsible for development and inheritable traits. (aboutdarwin.com)
• Breaks in DNA strands also occur naturally when chromosomes exchange genetic material during cell division. (medlineplus.gov)
• Efficient repair of damaged DNA strands helps maintain the stability of the cell's genetic information. (medlineplus.gov)
• We found some articles related to environmental interactions with inherited genotype and others on environmental exposures that damage genetic material and initiate molecular pathways of pathogenesis. (cdc.gov)

Efferent visual pathway3

• Affected individuals may experience problems with how they see the world (afferent visual pathway symptoms) and/or how smoothly and synchronously their eyes move together (efferent visual pathway disorders). (medscape.com)
• Neuro-ophthalmic manifestations are frequently encountered in multiple sclerosis (MS). Affected individuals may experience problems with how they see the world (afferent visual pathway symptoms) and/or how their eyes move together (efferent visual pathway disorders). (medscape.com)
• Because patients with MS who have visual symptoms tend to seek ophthalmic attention, eye care experts play a vital role in the localization of afferent and efferent visual pathway problems that may either represent the first clinical manifestation of MS or affect a patient with a well-established diagnosis. (medscape.com)

Enzymes7

• Thankfully, our bodies have dedicated enzymes and pathways which can glue our broken DNA back together through several different mechanisms, known as DNA repair pathways. (anxiety-stress-management.com)
• What was so beautiful and kind of elegant about the whole discovery is that there are two different enzymes alternating between pathway steps and helping each other out. (anxiety-stress-management.com)
• These are relatively mild damages that can be easily repaired by specialized enzymes that can seal the break and restore the integrity of the DNA molecule. (globalhealthnewswire.com)
• Enzymes can stitch the dangling ends back together, which often results in one or more bases -- the building blocks of DNA -- being added or deleted, disrupting the function of the gene. (sciencedaily.com)
• Alternatively, other enzymes can patch the break with a single strand of DNA that matches the DNA sequence upstream and downstream of the cut. (sciencedaily.com)
• The course plot for the saga of replication involves an array of characters, including enzymes like DNA polymerase, working tirelessly as diligent scribes, replicating each chapter accurately from the DNA template. (aboutdarwin.com)
• All of the enzymes in these three pathways are thoroughly described in reference 3. (blogspot.com)

Metabolic pathways1

• RUNX3 , STAT4 , NFKB1 ) and metabolic pathways (e.g. (biomedcentral.com)

Lagging-strand2

• On the leading strand, replication occurs continuously in a 5 to 3 direction, whereas on the lagging strand, DNA replication occurs discontinuously by synthesis and joining of short Okazaki fragments. (kegg.jp)
• Normally, during replication of the lagging-strand DNA template, an RNA primer is removed either by an RNase H or by the 5 to 3 exonuclease activity of DNA pol I, and the DNA ligase joins the Okazaki fragments. (kegg.jp)

Polymerase theta-mediated1

• Susanna Stroik, PhD, and Dale Ramsden, PhD, both researchers in the Department of Biochemistry and Biophysics in the UNC School of Medicine and the UNC Lineberger Comprehensive Cancer Center, have pieced together the lesser-known DNA repair pathway, called polymerase theta-mediated end joining (TMEJ). (anxiety-stress-management.com)

Damage induced3

• Whether the elevated TIGAR expression protects DNA damage induced by chemotherapeutic agents or hypoxia has not been explored. (nature.com)
• Such dichotomous kinetics implicate additional rate-limiting steps that are essential for DNA-damage-induced inflammation. (nature.com)
• Using this system, we showed that ATRIP was crucial for DNA damage-induced FANCD2 monoubiquitination and FANCI phosphorylation. (elsevierpure.com)

Homology Direct2

• Eukaryotic cells repair the DSBs by the fast but potentially mutagenic Non-Homologous End Joining (NHEJ), and by the accurate Homology Directed Repair (HDR) pathways. (europa.eu)
• The latter, homology-directed repair, happens more frequently in some types of cells than others, and requires the presence of a piece of DNA that can be used to patch the break. (sciencedaily.com)

Enzymatic pathway1

• Generally, DNA replication follows a multistep enzymatic pathway. (kegg.jp)

Intracellular3

• Localization of DNA to the cytosol is associated with tumorigenesis, viral infection, and invasion by some intracellular bacteria. (wikipedia.org)
• Animal models and humans lacking key DNA nucleases, such as Trex1/Dnase3, accumulate intracellular DNA and develop progressive autoimmunity marked by increased Type-I Interferon (IFN) expression and inflammatory signatures. (harvard.edu)
• We then implement the pathway in a photosynthetic organism Synechococcus elongates PCC7942, and show that it increases the intracellular acetyl-CoA pool and enhances bicarbonate assimilation by roughly 2-fold. (osti.gov)

Fanconi2

• Scientists discovered that a well-known DNA repair pathway, the Fanconi anemia pathway, surprisingly plays a key role in repairing double-strand DNA breaks created by CRISPR-Cas9. (sciencedaily.com)
• The Fanconi anaemia (FA) pathway represents a key DDR process which remains relatively inactive in normal brain, but is re-activated in glioblastoma, raising its value as a foundational target for cancer-specific treatment. (whiterose.ac.uk)

Cellular2

• One key cellular consequence of hypoxic stress is the regulation of DNA repair pathways, which contributes to the genomic instability and mutator phenotype observed in human cancers. (bibbase.org)
• Anomalies within the cellular DNA damage response (DDR) contribute to the treatment refractory nature of this devastating brain tumour with difficult-to-treat glioblastoma stem cell (GSC) subpopulations reported to exhibit heightened activity in various DDR processes. (whiterose.ac.uk)

Mechanisms5

• Yet, to fully understand the mechanisms of DNA synthesis all intermediate structures need to be identified. (elifesciences.org)
• The proposed studies represent a rigorous and comprehensive investigation into the mechanisms of cytosolic DNA sensing and will dramatically advance our understanding of the molecular basis of innate immunity against viral infection. (grantome.com)
• There are various repair mechanisms in our cells, each tailored to the type of DNA damage. (globalhealthnewswire.com)
• Paralleling the intra-tumor heterogeneity of hypoxia, the effects of hypoxia on DNA repair occur through diverse mechanisms. (bibbase.org)
• However, a model where the pathways are entwined was found to effectively fit without needing additional mechanisms. (bvsalud.org)

Cytosolic6

• The cGAS - STING pathway acts to detect cytosolic DNA and induce an immune response. (wikipedia.org)
• One way cytosolic DNA is sensed is via the cGAS/STING pathway, specifically by the cyclic-GMP-AMP synthase (cGAS). (wikipedia.org)
• cGAS is found at the plasma membrane and is responsible for detecting cytosolic double stranded DNA, normally found in the cell nucleus, in order to stimulate production of IFN-β. (wikipedia.org)
• Upon directly binding cytosolic DNA, cGAS forms dimers to catalyze production of 2'3'-cGAMP from ATP and GTP. (wikipedia.org)
• This activity is dependent on cytosolic DNA. (wikipedia.org)
• Recent studies showed that cytosolic DNA sensing and subsequent STING activation also leads to induction of autophagy, a degradative pathway involved in metabolic recycling and regulation of infections and immunity. (fabiodisconzi.com)

Methylation7

• We longitudinally analyzed genome-wide DNA methylation changes in CD4 + T cells from lymph node and blood, using arrays. (biomedcentral.com)
• DNA methylation changes after SIV infection were more pronounced in lymph nodes than blood and already detected in primary infection. (biomedcentral.com)
• Altered DNA methylation was confirmed in blood and lymph node CD4 + T cells in viremic macaques but was notably absent from SIV controller macaques. (biomedcentral.com)
• 6) 4) de Vega et al: DNA methylation Modifications associated with CFS. (blogspot.com)
• 7) Trivedi et al: Identification of ME/CFS - associated DNA methylation patterns. (blogspot.com)
• 8) de Vega et al: Integration of DNA methylation & health scores identifies subtypes in ME/CFS. (blogspot.com)
• In this review, we identified articles aligning with the traditional epidemiologic concept of GxE, as well as several associated with newer biomarkers of exposure, such as DNA methylation (epigenetics) and telomere length. (cdc.gov)

Enzyme9

• Scientist often use a technique called X-ray crystallography to study intermediate structures of frozen polymerase crystals as the enzyme constructs DNA. (elifesciences.org)
• Together, these structures provide new insight into the mechanism of DNA synthesis and highlight the dynamic nature of the finger subdomain in the enzyme active site. (elifesciences.org)
• In the latest example, University of California, Berkeley, scientists found that people's assumptions about how cells repair the genome after the Cas9 enzyme snips DNA are wrong. (sciencedaily.com)
• The star enzyme that plays a critical role in synthesizing new DNA strands by following the older DNA as a template. (aboutdarwin.com)
• This enzyme unwinds the double-stranded DNA, paving the way for replication. (aboutdarwin.com)
• Microarray technologies provide analysis of tens of thousands of molecules for a variety of assays, including drug binding, molecular interactions, enzyme activity and pathway identification. (bccresearch.com)
• NAMPT is an enzyme in the salvage pathway. (blogspot.com)
• NADSYN1 is an enzyme in the Preiss-Handler pathway. (blogspot.com)
• QPRT is an enzyme the de novo pathway. (blogspot.com)

Strands8

• DNA molecules consist of two separate strands that spiral around each other to form a structure called the double helix. (elifesciences.org)
• When a double stranded break occurs, both strands of DNA are cut at the same spot, much like scissors severing a braid of hair. (anxiety-stress-management.com)
• Polymerase theta acts quickly, grabbing the two single strands of DNA, matching up the closest base pairs to the break, and holding them together. (anxiety-stress-management.com)
• Polymerase delta jumps in to cut the extraneous flaps, giving polymerase theta enough room to start synthesizing new DNA to fill in gaps in the DNA strands. (anxiety-stress-management.com)
• As DNA is a molecule consisting of two strands, either one or both of the strands can be damaged. (globalhealthnewswire.com)
• Single-strand break (SSB), occur when one of the two strands of DNA is damaged or broken. (globalhealthnewswire.com)
• On the other hand, a double-strand break (DSB) refers to when both strands of DNA are damaged. (globalhealthnewswire.com)
• These are essentially the core building blocks of new DNA strands. (aboutdarwin.com)

Synthesis pathway1

• Here we report five crystal structures of DNA polymerase I that capture new conformations for the polymerase translocation and nucleotide pre-insertion steps in the DNA synthesis pathway. (elifesciences.org)

Subunit2

• DNA polymerase epsilon, which is involved in DNA repair and replication, is composed of a large catalytic subunit and a small accessory subunit. (nih.gov)
• Purification, cDNA cloning, and gene mapping of the small subunit of human DNA polymerase epsilon. (nih.gov)

TMEJ4

• Out of all DNA repair pathways, TMEJ has been the most elusive. (anxiety-stress-management.com)
• Over the next 15 years, multiple labs, including the Wood, Ramsden, and Gupta labs (also at Lineberger Comprehensive Cancer Center), were able to link polymerase theta to DNA repair (TMEJ) and cancer. (anxiety-stress-management.com)
• With the help of these collaborators, Stroik was able to use a wide variety of cutting-edge experimental approaches to fill in the gaps in our understanding of the TMEJ pathway. (anxiety-stress-management.com)
• Since many cancers make use of the TMEJ pathway to keep tumors alive, many researchers have investigated creating drugs that can interfere with the pathway, essentially preventing cancer from repairing itself, leading to its eventual demise. (anxiety-stress-management.com)

Kinase2

• ATR kinase activates the S-phase checkpoint when replication forks stall at sites of DNA damage. (elsevierpure.com)
• Together, our findings identify ATR as the kinase responsible for activating the FA pathway of DNA repair. (elsevierpure.com)

Mechanism5

• Thus, one mechanism of epirubicin combined TACE treatment for HCC was through induction of synergistic DNA damage. (nature.com)
• High resolution crystal structures of DNA polymerase intermediates are needed to study the mechanism of DNA synthesis in cells. (elifesciences.org)
• HSER in normal and XP-C cell lines, but not CS-A, XP-A, XP-D or XP-G cells, suggests that HS treatment can enhance the repair of UV-damaged DNA through an enhancement of transcription coupled repair (TCR) or a mechanism which involves the TCR pathway. (mcmaster.ca)
• In the proposed studies, the PIs will investigate the molecular mechanism of the cGAS-STING pathway, especially how ligand binding by STING initiates downstream signaling events. (grantome.com)
• Until now, most researchers thought that a specific type of DNA damage is only repaired by its corresponding DNA repair mechanism. (globalhealthnewswire.com)

Regulation2

• The Cdk5-AMT signal pathway involved in regulation of DDR by TIGAR defines a new role of TIGAR in cancer cell survival and it suggests that TIGAR may be a therapeutic target for cancers. (nature.com)
• NAD+) pathway is closely associated with regulation of immune cells toward less inflammatory phenotypes and may exert neuroprotective effects. (blogspot.com)

NHEJ3

• Mechanistic Modelling of Slow and Fast NHEJ DNA Repair Pathways Following Radiation for G0/G1 Normal Tissue Cells. (bvsalud.org)
• Non-homologous end joining (NHEJ) is the major DSB-repair pathway available throughout the cell cycle and, recently, has been hypothesised to consist of a fast and slow component in G0/G1. (bvsalud.org)
• It has been shown that DaMaRiS is a useful tool when analysing the connections between resection-dependent and independent NHEJ repair pathways and robustly matches with experimental results from several sources. (bvsalud.org)

Recombination1

• Elevated levels of reactive oxygen species as well as impaired homologous recombination repair underlie this DNA damage. (bepress.com)

Including DNA double-strand1

• On a longer timescale, hypoxia leads to transcriptional and/or translational downregulation of most DNA repair pathways including DNA double-strand break repair, mismatch repair, and nucleotide excision repair. (bibbase.org)

Hypoxia6

• This study investigated the role of TIGAR in DNA damage response (DDR) induced by genotoxic drugs and hypoxia in tumor cells. (nature.com)
• Epirubicin, a DNA damaging anticancer agent and CoCl 2 , which was used to imitate hypoxia condition, was applied to induce DNA damage in TIGAR knockdown HepG2 cells. (nature.com)
• The samples also differed in the basal activity of the hypoxia pathway: the highest level was detected in TP53-mutant samples, followed by profile II and profile I. Our study suggests that wild-type TP53 CLL cells with less phosphorylated p53 show TP53-mutant-like behavior after DNA damage. (muni.cz)
• p53 hypophosphorylation and the related lower ability to respond to DNA damage are linked to ATM locus defects and the higher basal activity of the hypoxia pathway. (muni.cz)
• Acutely, hypoxia activates DNA damage signaling pathways, primarily via post-translational modifications. (bibbase.org)
• article{scanlon_multifaceted_nodate, title = {Multifaceted control of {DNA} repair pathways by the hypoxic tumor microenvironment}, issn = {1568-7864}, url = {http://www.sciencedirect.com/science/article/pii/S1568786415001226}, doi = {10.1016/j.dnarep.2015.04.030}, abstract = {Hypoxia, as a pervasive feature in the microenvironment of solid tumors, plays a significant role in cancer progression, metastasis, and ultimately clinical outcome. (bibbase.org)

Single-stranded6

• Because the mitochondrial DNA of P. falciparum appeared to be the target of gelonin's cytotoxic activity and contained single-stranded regions, we investigated the activity of gelonin on single stranded DNA. (jefferson.edu)
• Both the native and recombinant forms of gelonin were found to cause the degradation of single stranded DNA. (jefferson.edu)
• This activity was unique, as there is no other report of a DNA glycosylase/AP lyase that acts on single stranded DNA. (jefferson.edu)
• It is likely that this pathway utilized a flap endonuclease to process the single-stranded DNA that occurs during repair synthesis. (jefferson.edu)
• However, this often leaves some residual flaps of single stranded DNA at the ends. (anxiety-stress-management.com)
• Researchers often supply a single-stranded piece of DNA and hope that the cell uses it to replace the faulty sequence with the new one. (sciencedaily.com)

Inflammatory3

• Here we show that cell cycle progression through mitosis following double-stranded DNA breaks leads to the formation of micronuclei, which precede activation of inflammatory signalling and are a repository for the pattern-recognition receptor cyclic GMP-AMP synthase (cGAS). (nature.com)
• Figure 2: Progression through mitosis underlies inflammatory pathway activation. (nature.com)
• Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. (nature.com)

Chromosome2

• DNA breaks and chromosome pulverization from errors in mitosis. (nature.com)
• It's quite an intricate dance aimed at making sure every new chromosome is equipped with one old and one new strand of DNA - this is referred to as semi-conservative replication. (aboutdarwin.com)

Helicase1

• At the DNA replication fork, a DNA helicase (DnaB or MCM complex) precedes the DNA synthetic machinery and unwinds the duplex parental DNA in cooperation with the SSB or RPA. (kegg.jp)

CRISPR-Cas92

• And it could help researchers boost the efficiency with which cells insert new DNA into the genome -- to replace a harmful mutation with the correct DNA sequence, for example -- and generally tweak CRISPR-Cas9 editing to get the desired outcome. (sciencedaily.com)
• CRISPR-Cas9 is revolutionary because of the precision with which it homes in on a specific DNA sequence out of billions in the genome and cleaves the double-stranded DNA molecule. (sciencedaily.com)

Organism1

• DNA is well known as the blueprint of life, necessary for an organism to facilitate living processes. (globalhealthnewswire.com)

Progression1

• Another pathway, TGF-β signaling pathway, appears to play a part in the progression of diabetes, insulin resistance, and autoimmunity in both type 1 and 2 diabetes and complications in diabetes. (frontiersin.org)

Modulation4

• The discoveries of the hypoxic modulation of DNA repair pathways have highlighted many potential ways to target susceptibilities of hypoxic cancer cells. (bibbase.org)
• Consequently, several therapeutic agents such as adiponectin, ezetimibe, GABA tea, geniposide, liraglutide, guava extract, and vitamin D were shown to inhibit diabetes and its complications through modulation of the autophagy pathway. (frontiersin.org)
• Anti-diabetic drugs such as metformin and rosiglitazone have been reported to act via modulation of the TGF-β signaling pathway. (frontiersin.org)
• Natural agents including compounds as resveratrol, puerarin, curcumin, hesperidin and silymarin, and extracts of propolis, Lycopus lucidus , and Momordica charantia have been shown to combat diabetes via modulation of TGF-β signaling pathway. (frontiersin.org)

Therapies4

• Understanding how polymerases modify their form while making DNA copies could lead to better therapies for diseases in which this process has become faulty, like cancer. (elifesciences.org)
• Research using the model pointed toward potential pathways to improve therapies, including DNA damage repair pathways which are well-known for their involvement in other types of cancer. (bioengineer.org)
• Introduction: Glioblastoma represent around half of newly diagnosed glial tumours and continue to portend poor survival (median 15.6 months) despite maximal safe surgical resection followed by DNA-damaging adjuvant therapies. (whiterose.ac.uk)
• This thesis therefore, considers whether combined targeting of the FA pathway and interconnected DDR processes could form a basis for new, effective multimodal therapies. (whiterose.ac.uk)

Therapeutic3

• My goal is to decipher the 53BP1-Shieldin induced block and then assess Shieldin pathway as a possible therapeutic target to increase the frequency of HDR after CRISPR-Cas cleavage. (europa.eu)
• Furthermore, patient-derived GSC populations, which drive therapeutic resistance, display high FA pathway expression relative to paired bulk tumour cell populations. (whiterose.ac.uk)
• Conclusion: Simultaneously targeting the FA pathway and interconnected DDR processes represents an appealing therapeutic strategy. (whiterose.ac.uk)

Gene expression2

• This second volume of the Metabolic Pathway Engineering Handbook delves into evolutionary tools and gene expression tools for metabolic pathway engineering. (taylorfrancis.com)
• Results: Elevated FA pathway gene expression in gliomas is associated with poor survival. (whiterose.ac.uk)

Vitro1

• We first functionally demonstrate the design of the MCG pathway in vitro and in Escherichia coli. (osti.gov)

Ligase1

• FEN 1 and RNase H1 remove the RNA from the Okazaki fragments and DNA ligase I joins the DNA. (kegg.jp)

Double-strand breaks1

• Furthermore, comparison of a/b ratio enhancement suggests dual-DDRi strategies fundamentally alter the response of GSCs, whilst single cell gel electrophoresis and immunofluorescence studies suggest FA pathway-based DDRi combinations substantially delay the resolution of IR-induced DNA strand breaks at 6 hours post-treatment, with increased persistent DNA double strand breaks at 24 hours. (whiterose.ac.uk)

Occurs1

• Alternate pathway activation occurs when components of microbial cell surfaces (eg, yeast walls, bacterial cell wall lipopolysaccharide [endotoxin]) or immunoglobulin (eg, nephritic factor, aggregated IgA) cleave small amounts of C3. (msdmanuals.com)

Viral6

• Here, for the first time, we discover that the human SUMOylation pathway is essential for the IBV viral life cycle. (mdpi.com)
• The Molecular Basis of Viral DNA Sensing through the cGAS-STING Pathway The innate immune response is the first line of defense against invading pathogens. (grantome.com)
• Viral nucleic acids, such as DNA and RNA, serve as danger signals that induce potent immune responses in infected cells. (grantome.com)
• It is activated by viral DNA and catalyzes the synthesis of a noncanonical cyclic dinucleotide 2? (grantome.com)
• These comprehensive structural and functional studies significantly advanced our understanding about how the innate immune system responds to viral DNA at molecular level. (grantome.com)
• The activation of the cGAS-STING pathway by viral DNA results in the expression of type I interferons, a key family of antiviral cytokines. (grantome.com)

STING1

• Built-upon our strong preliminary studies, the proposed research will elucidate the molecular bases of several key steps of the cGAS-STING pathway with the following aims: 1). (grantome.com)

Autophagy2

• The prominent role of autophagy signaling pathway was supported by the alteration of autophagy markers in patients and animal models of T1DM, T2DM, and gestational diabetes. (frontiersin.org)
• EU H2020 Project 'PATHAUTOBIO (Uncovering the pathway of DNA-induced autophagy and its biological functions. (fabiodisconzi.com)

Functionally1

• This pathway otherwise resembles the classical pathway structurally and functionally. (msdmanuals.com)

Genomic1

• Genomic DNA was isolated and amplified using nature for these variants. (cdc.gov)

Converts2

• The phosphopentose pathway (PPP), which converts glucose-6-phosphate to ribose-5-phosphate for synthesis of nucleotides and NADPH to reduce DNA damage caused by ROS was reported to be activated in DDR 2 . (nature.com)
• This pathway converts a C3 metabolite to two acetyl-CoA by fixation of one additional CO2 equivalent, or assimilates glyoxylate, a photorespiration intermediate, to produce acetyl-CoA without net carbon loss. (osti.gov)

Cells9

• In normal cells, DNA is confined to the nucleus or mitochondria. (wikipedia.org)
• To define a role of TIGAR in DNA damage, TIGAR expression was knocked down with siRNA in HepG2 cells. (nature.com)
• DNA damage in HepG2 cells after TIGAR knockdown with or without treatment of epirubicin or CoCl 2 was detected by Comet assay. (nature.com)
• Cells with even one mutant copy of RB1 have increased basal levels of DNA damage and increased mitotic errors. (bepress.com)
• Now that we know more about this pathway, scientists could, in theory, produce a drug that could disrupt key pieces of the pathway in cancer cells, as opposed to using conventional chemotherapies that destroy healthy cells along with the cancer. (anxiety-stress-management.com)
• Cells maintain genome integrity by having various pathways to repair DSBs. (globalhealthnewswire.com)
• Both processes are a bit mysterious, however, and no one knows why some cells readily patch in DNA while others do so infrequently. (sciencedaily.com)
• The cells were then intracellularly stained with 5 µg/ml anti-DNA-PKcs phospho (Thr2609) (clone 10B1) antibody in blocking buffer overnight at 4°C followed by staining with Alexa Fluor® 488 conjugated goat anti-mouse IgG antibody (clone Poly4053) for one hour at room temperature. (biolegend.com)
• The ME metabolic trap hypothesis predicts dysregulated Trp-Kyn- pathway in immune cells from ME patients (11). (blogspot.com)

Sequence1

• Gene editing techniques exploit the HDR to modify the DNA to the desired sequence. (europa.eu)

Transcription1

• DNA Replication and RNA Transcription, although seemingly complex terms, hold within them concepts that are beautifully precise, methodical - true marvels of nature. (aboutdarwin.com)