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*  To cause genomic instability particularly at chromosome loci that are intrinsically | www.nrtisinhibitor.com
To cause genomic instability particularly at chromosome loci that are intrinsically difficult to replicate because of the complexity of secondary structures or
http://www.nrtisinhibitor.com/2017/08/08/to-cause-genomic-instability-particularly-at-chromosome-loci-that-are-intrinsically/
*  Reducing MCM levels in human primary T cells during the G0-G1 transition causes genomic instability during the first cell cycle...
DNA replication is tightly regulated, but paradoxically there is reported to be an excess of MCM DNA replication proteins over the number of replication origins. Here, we show that MCM levels in primary human T cells are induced during the G(0)--,G(1) transition and are not in excess in proliferating cells. The level of induction is critical as we show that a 50% reduction leads to increased centromere separation, premature chromatid separation (PCS) and gross chromosomal abnormalities typical of genomic instability syndromes. We investigated the mechanisms involved and show that a reduction in MCM levels causes dose-dependent DNA damage involving activation of ATR & ATM and Chk1 & Chk2. There is increased DNA mis-repair by non-homologous end joining (NHEJ) and both NHEJ and homologous recombination are necessary for Mcm7-depleted cells to progress to metaphase. Therefore, a simple reduction in MCM loading onto DNA, which occurs in cancers as a result of aberrant cell cycle ...
http://eprints.kingston.ac.uk/38269/
*  Human THO-Sin3A interaction reveals new mechanisms to prevent R‐loops that cause genome instability | The EMBO Journal
R‐loops, formed by co‐transcriptional DNA-RNA hybrids and a displaced DNA single strand (ssDNA), fulfill certain positive regulatory roles but are also a source of genomic instability. One key cellular mechanism to prevent R‐loop accumulation centers on the conserved THO/TREX complex, an RNA‐binding factor involved in transcription elongation and RNA export that contributes to messenger ribonucleoprotein (mRNP) assembly, but whose precise function is still unclear. To understand how THO restrains harmful R‐loops, we searched for new THO‐interacting factors. We found that human THO interacts with the Sin3A histone deacetylase complex to suppress co‐transcriptional R‐loops, DNA damage, and replication impairment. Functional analyses show that histone hypo‐acetylation prevents accumulation of harmful R‐loops and RNA‐mediated genomic instability. Diminished histone deacetylase activity in THO‐ and Sin3A‐depleted cell lines correlates with ...
http://emboj.embopress.org/content/36/23/3532
*  Genome instability - Wikipedia
Genome instability (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneuploidy. Genome instability does occur in bacteria. In multicellular organisms genome instability is central to carcinogenesis, and in humans it is also a factor in some neurodegenerative diseases such as amyotrophic lateral sclerosis or the neuromuscular disease myotonic dystrophy. The sources of genome instability have only recently begun to be elucidated. A high frequency of externally caused DNA damage can be one source of genome instability since DNA damages can cause inaccurate translesion synthesis past the damages or errors in repair, leading to mutation. Another source of genome instability may be epigenetic ...
https://en.wikipedia.org/wiki/Genome_instability
*  DNA damage repair | 2018 NCRI Cancer Conference
Large-scale genomic studies have demonstrated that approximately 50% of high-grade serous ovarian cancers (HGSOCs) harbor genetic and epigenetic alterations in homologous recombination repair (HRR) pathway genes. The most commonly altered HRR genes are BRCA1 and BRCA2, followed by other Fanconi Anemia genes. Loss of HRR causes genomic instability, hyperdependence on alternative DNA repair mechanisms, and enhanced sensitivity to PARP-inhibitors (PARPi) through the mechanism of synthetic lethality. PARP inhibitor resistance has emerged as a vexing clinical problem for the treatment of BRCA1/2 deficient tumors. The most prevalent mechanism of PARPi resistance is secondary events that cancel the original HRR alteration and restore HRR proficiency. PARPi resistance also develops without restoration of HRR proficiency through enhanced replication fork (RF) stabilization. We have recently made the surprising observation that BRCA2-deficient tumor cells can ...
https://conference.ncri.org.uk/programme_entry/dna-damage-repair/
*  BRIT1 Allows DNA Repair Teams Access To Damaged Sites - Redorbit
Tumor-suppressor recruits help to overcome a barrier and fix cancer-causing defects. Like a mechanic popping the hood of a car to get at a faulty engine, a tumor-suppressing protein allows cellular repair mechanisms to pounce on damaged DNA by overcoming a barrier to DNA access.. Reporting online at Nature Cell Biology this week, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center shows that BRIT1 connects with another protein complex to relax DNA's tight packaging at the site of the damage.. "Relaxing this barrier allows two different DNA repair pathways greater access to the damage, preventing flawed DNA from being passed on as the cell divides, which causes genomic instability leading to cancer," said senior author Shiaw-Yih Lin, Ph.D., assistant professor in M. D. Anderson's Department of Systems Biology.. BRIT1 is under-expressed in human ovarian, breast and prostate cancer cell lines. Lin and colleagues previously showed that the ...
http://www.redorbit.com/news/health/1708573/brit1_allows_dna_repair_teams_access_to_damaged_sites/
*  Fanconi anemia, complementation group J*del
Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder that causes genomic instability. Characteristic clinical features include developmental abnormalities in major organ systems, early-onset bone marrow failure, and a high predisposition to cancer. The cellular hallmark of FA is hypersensitivity to DNA crosslinking agents and high frequency of chromosomal aberrations pointing to a defect in DNA repair (summary by {1:Deakyne and Mazin, 2011}). For additional general information and a discussion of genetic heterogeneity of Fanconi anemia, see {227650 ...
http://www.diseaseinfosearch.org/Fanconi+anemia%2C+complementation+group+J/8416
*  Characterisation of DNA-protein crosslink proteolysis repair | Department of Oncology
DNA-protein crosslinks (DPCs) are under-investigated DNA lesions caused by the covalent attachment of proteins to DNA. DPCs are induced by various endogenous chemicals like aldehydes or by chemotherapeutic drugs. Little is known about how cells repair DPCs and thus acquire resistance to DPC-induced chemotherapy. However, the persistence of DPCs causes genomic instability and cancer. We recently discovered a human syndrome (Ruijs-Aalfs or SPARTAN syndrome) related to the defective DPC repair pathway.
https://www.oncology.ox.ac.uk/project/characterisation-dna-protein-crosslink-proteolysis-repair
*  Leicester Research Archive: DNA methylation, cell differentiation and genetic factors involved in radiosensitivity.
Despite its benefits in cancer treatment, ionising radiation (IR) can induce a series of adverse acute and/or long term effects. Studies on A-bomb survivors and radiotherapy patients have shown that acute whole-body exposure results in an increased risk for radiation-induced Acute Myeloid Leukaemia (r-AML), a bone marrow (BM) malignancy; whereas local-radiotherapy patients run the risk of developing acute and/or long term normal tissue reactions. Irradiated BM cells manifest persistent radiation-induced genomic instability. BM is one of the most susceptible tissues to radiation-induced cancer and one of the most radiosensitive tissues, which proposes a link between cancer susceptibility, genomic instability and radiosensitivity. The exact mechanism by which exposure of BM cells to IR leads to malignant transformation is still unclear, but the non-targeted nature of radiation-induced damage and genomic ...
https://lra.le.ac.uk/handle/2381/4150
*  IJMS | Free Full-Text | Oncogene-Induced Replication Stress Drives Genome Instability and Tumorigenesis
Genomic instability plays a key role in driving cancer development. It is already found in precancerous lesions and allows the acquisition of additional cancerous features. A major source of genomic instability in early stages of tumorigenesis is DNA replication stress. Normally, origin licensing and activation, as well as replication fork progression, are tightly regulated to allow faithful duplication of the genome. Aberrant origin usage and/or perturbed replication fork progression leads to DNA damage and genomic instability. Oncogene activation is an endogenous source of replication stress, disrupting replication regulation and inducing DNA damage. Oncogene-induced replication stress and its role in cancer development have been studied comprehensively, however its molecular basis is still unclear. Here, we review the current understanding of replication regulation, its potential disruption and how ...
http://www.mdpi.com/1422-0067/18/7/1339
*  Dysregulation of DNA polymerase κ recruitment to replication forks results in genomic instability | The EMBO Journal
Results from our study provide mechanistic insights into how USP1 maintains genomic stability in human cells. Unexpectedly, a major genome stabilizing function of USP1 is to suppress sporadic PCNA ubiquitination during the normal DNA replication process. Failure to reduce the pool of ubiquitinated PCNA leads to the aberrant recruitment of Polκ to the replication fork. Misuse of Polκ during DNA replication results in a slower replication fork, micronuclei formation, and genomic instability. While it is known that the FA pathway can also be regulated by USP1, it is still unclear how USP1 is directly involved in mediating DNA crosslink repair and the maintenance of genomic stability through the function of FA proteins. On the other hand, the FA pathway likely plays a critical role in preventing further replication stress‐induced DNA damage in USP1‐deficient cells. In summary, our data demonstrate that the genomic ...
http://emboj.embopress.org/content/31/4/908
*  Sandy Chang, MD, PhD > Yale Cancer Center | Yale School of...
Dr. Chang's research program focuses on telomeres,repetitive DNA sequences at the ends of chromosomes critically important for the maintenance of genome stability. Perturbation of telomere length results in telomere dysfunction, leading to increased genomic instability that can promote early aging and cancer development. Dr. Chang's laboratory was the first togenerate a faithful mouse model of Werner Syndrome (WS). This rare disease strikes individuals in their 30s and is marked by the development of aging phenotypes and early onset of cancer.. Dr. Chang found that when WRN deficiency is coupled withtelomere dysfunction, the combination increases genomic instability, pre-matureaging and increased tumorigenesis. In addition, his findings conclusively demonstrate that telomere status plays an important role in the development of premature aging pathologies observed in WS patients. With this mouse model, Dr. Chang's laboratory has also ...
http://medicine.yale.edu/cancer/research/people/s_chang-2.profile
*  Sandy Chang, MD, PhD > MD-PhD Program | Yale School of...
Dr. Chang's research program focuses on telomeres,repetitive DNA sequences at the ends of chromosomes critically important for the maintenance of genome stability. Perturbation of telomere length results in telomere dysfunction, leading to increased genomic instability that can promote early aging and cancer development. Dr. Chang's laboratory was the first togenerate a faithful mouse model of Werner Syndrome (WS). This rare disease strikes individuals in their 30s and is marked by the development of aging phenotypes and early onset of cancer.. Dr. Chang found that when WRN deficiency is coupled withtelomere dysfunction, the combination increases genomic instability, pre-matureaging and increased tumorigenesis. In addition, his findings conclusively demonstrate that telomere status plays an important role in the development of premature aging pathologies observed in WS patients. With this mouse model, Dr. Chang's laboratory has also ...
http://medicine.yale.edu/mdphd/people/s_chang-2.profile
*  Sandy Chang, MD, PhD | Yale School of Medicine
Dr. Chang's research program focuses on telomeres,repetitive DNA sequences at the ends of chromosomes critically important for the maintenance of genome stability. Perturbation of telomere length results in telomere dysfunction, leading to increased genomic instability that can promote early aging and cancer development. Dr. Chang's laboratory was the first togenerate a faithful mouse model of Werner Syndrome (WS). This rare disease strikes individuals in their 30s and is marked by the development of aging phenotypes and early onset of cancer.. Dr. Chang found that when WRN deficiency is coupled withtelomere dysfunction, the combination increases genomic instability, pre-matureaging and increased tumorigenesis. In addition, his findings conclusively demonstrate that telomere status plays an important role in the development of premature aging pathologies observed in WS patients. With this mouse model, Dr. Chang's laboratory has also ...
http://medicine.yale.edu/intranet/facultybydept/s_chang-2.profile
*  Sandy Chang, MD, PhD | Yale School of Medicine
Dr. Chang's research program focuses on telomeres,repetitive DNA sequences at the ends of chromosomes critically important for the maintenance of genome stability. Perturbation of telomere length results in telomere dysfunction, leading to increased genomic instability that can promote early aging and cancer development. Dr. Chang's laboratory was the first togenerate a faithful mouse model of Werner Syndrome (WS). This rare disease strikes individuals in their 30s and is marked by the development of aging phenotypes and early onset of cancer.. Dr. Chang found that when WRN deficiency is coupled withtelomere dysfunction, the combination increases genomic instability, pre-matureaging and increased tumorigenesis. In addition, his findings conclusively demonstrate that telomere status plays an important role in the development of premature aging pathologies observed in WS patients. With this mouse model, Dr. Chang's laboratory has also ...
http://medicine.yale.edu/news/s_chang-2.profile?source=news
*  Estrogen potentiates reactive oxygen species (ROS) tolerance to initiate carcinogenesis and promote cancer malignant...
Estrogen-mediated high reactive oxygen species (ROS) tolerance plays an important role in driving carcinogenesis. ROS overproduction acts as the significant effector to increase genomic instability...
https://link.springer.com/article/10.1007/s13277-015-4370-6
*  Evidence for Active Maintenance of Inverted Repeat Structures Identified by a Comparative Genomic Approach
Inverted repeats have been found to occur in both prokaryotic and eukaryotic genomes. Usually they are short and some have important functions in various biological processes. However, long inverted repeats are rare and can cause genome instability. Analyses of C. elegans genome identified long, nearly-perfect inverted repeat sequences involving both divergently and convergently oriented homologous gene pairs and complete intergenic sequences. Comparisons with the orthologous regions from the genomes of C. briggsae and C. remanei show that the inverted repeat structures are often far more conserved than the sequences. This observation implies that there is an active mechanism for maintaining the inverted repeat nature of the sequences.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0000262
*  The human synMuv-like protein LIN-9 is required for transcription of G2/M genes and for entry into mitosis - Osterloh - 2006 -...
Shepard JL, Amatruda JF, Stern HM, Subramanian A, Finkelstein D, Ziai J, Finley KR, Pfaff KL, Hersey C, Zhou Y, Barut B, Freedman M, Lee C, Spitsbergen J, Neuberg D, Weber G, Golub TR, Glickman JN, Kutok JL, Aster JC, Zon LI (2005) A zebrafish bmyb mutation causes genome instability and increased cancer susceptibility. Proc Natl Acad Sci USA 102: 13194-13199 ...
http://onlinelibrary.wiley.com/doi/10.1038/sj.emboj.7601478/references
*  History Gene amplification is a frequent manifestation of genomic instability that - Therapeutic Applications of Kinase...
History Gene amplification is a frequent manifestation of genomic instability that plays a role in tumour progression and development of drug resistance. formation of micronuclei or nuclear buds which correlated with the removal of and increased sensitivity to MTX. These Indoximod findings indicate for the first time that NHEJ plays a specific role in DM formation and that increased MTX sensitivity of DM-containing cells depleted of DNA-PKcs results from removal. Conversely in HSR-containing cells we found no significant switch in the expression of NHEJ proteins. Depletion of DNA-PKcs experienced no effect on amplification and resulted in only a modest increase in sensitivity to MTX. Interestingly both DM-containing and HSR-containing cells exhibited decreased proliferation upon DNA-PKcs depletion. Conclusions We demonstrate a novel specific role for NHEJ in the formation of DMs but not HSRs in MTX-resistant cells and that NHEJ may be Indoximod targeted for the treatment of ...
http://www.antibodyassay.com/index.php/2016/10/21/history-gene-amplification-is-a-frequent-manifestation-of-genomic-instability-that/
*  Genomic Instability and Radiation Risk in Molecular Pathways to Colon Cancer - pdf descargar
Genomic Instability and Radiation Risk in Molecular Pathways to Colon Cancer. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
http://libros.duhnnae.com/2017/jun8/149843087783-Genomic-Instability-and-Radiation-Risk-in-Molecular-Pathways-to-Colon-Cancer.php
*  genomic instability
In a year of intriguing studies this is one of the more intriguing. Stress has been something of a keynote in CFS research lately and researchers now regularly employ different kinds of stress tests to provoke abnormalities in patients. But does this unusual response to stress make its way all into the DNA of our cells? The National CFIDS Foundation in collaboration with the Nancy Taylor Foundation is betting $133,000 that it does…. It looks like it might be a good bet. Dr. Henry Heng has been evolving a uique theory of 'genomic instability' for over a decade.… Read More. ...
http://phoenixrising.me/archives/tag/genomic-instability
*  Evidence on Structural Instability in Macroeconomic Time Series Relations
An experiment is performed to assess the prevalence of instability in univariate and bivariate macroeconomic time series relations and to ascertain whether various adaptive forecasting techniques successfully handle any such instability. Formal tests for instability and out-of-sample forecasts from sixteen different models are computed using a sample of 76 representative U.S. monthly postwar macroeconomic time series, constituting 5700 bivariate forecasting relations. The tests indicate widespread instability in univariate and bivariate autoregressive models. However, adaptive forecasting models, in particular time varying parameter models, have limited success in exploiting this instability to improve upon fixed-parameter or recursive autoregressive forecasts. ...
http://www.nber.org/papers/t0164
*  The Winnower | Open Scholarly Publishing
Correspondence re: Zimonjic et al. 2001. 'Derivation of human tumor cells in vitro without widespread genomic instability.' Cancer Res no. 61 (24):8838-44. Submitted to Cancer Research 8/19/2002, r... Read It Review It ...
https://thewinnower.com/keywords/aneuploidy
*  Five Hidden Signs of Instability
Author: Perry Nickelston. Title: Five Hidden Signs of Instability. Summary: If you work with patients long enough, you come to realize a few in-the-trenches facts. Here are five biggies that require constant consideration...
http://www.dynamicchiropractic.ca/mpacms/dc_ca/article.php?id=56095
*  Instability, Liquidity and World Money
Trouvez tous les livres de Schmeidler, Lacey - Instability, Liquidity and World Money. Sur eurolivre.fr,vous pouvez commander des livres anciens et neufs.COMPARER ET acheter IMMÉDIATEMENT au meilleur prix. 9783845404103
https://www.eurolivre.fr/livre/isbn/9783845404103.html