keyword
MENU ▼
Read by QxMD icon Read
search

atm mutated

keyword
https://www.readbyqxmd.com/read/28647894/keratin-gene-mutations-influence-the-keratinocyte-response-to-dna-damage-and-cytokine-induced-apoptosis
#1
Tina Zupancic, Gregor Sersa, Hans Törmä, Ellen Birgitte Lane, Harald Herrmann, Radovan Komel, Mirjana Liovic
The keratin filament cytoskeleton is vital to the normal function of epithelial cells. It provides structural support and regulates different aspects of cell metabolism. Mutations in keratins 5 and 14 cause a skin fragility disorder, epidermolysis bullosa simplex (EBS). Patients with severe EBS have an increased cumulative risk for basal cell carcinoma. In this study, we tested how keratin 5 and 14 mutant EBS patient-derived keratinocytes behave in the face of two different types of stressors that are able to induce cell death: ionizing radiation and cytokines TNF-α and TRAIL...
June 24, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28643015/the-role-of-screening-mri-in-the-era-of-next-generation-sequencing-and-moderate-risk-genetic-mutations
#2
REVIEW
Sarah Macklin, Jennifer Gass, Ghada Mitri, Paldeep S Atwal, Stephanie Hines
With the advent of next-generation sequencing, the ability to rapidly analyze numerous genes simultaneously has led to the creation of large cancer gene panels. Some of these genes, like BRCA1 and BRCA2, have been heavily researched and have well-established management guidelines. Other more newly established genes, like ATM, CHEK2, and PALB2, have previously had less robust research surrounding them which has limited the ability to create accurate risk estimates. With their inclusion on gene panels, there has been more pressure to produce management guidelines for patients discovered to carry pathogenic variants in these genes...
June 22, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28642860/ataxia-telangiectasia-mutated-atm-polymorphisms-and-risk-of-lung-cancer-in-a-chinese-population
#3
Ajay A Myneni, Shen-Chih Chang, Rungui Niu, Li Liu, Baoxing Zhao, Jianping Shi, Xiaoyou Han, Jiawei Li, Jia Su, Shunzhang Yu, Zuo-Feng Zhang, Lina Mu
BACKGROUND: The ataxia telangiectasia-mutated (ATM) gene has a key role in DNA repair including activation and stabilization of p53, which implicates the importance of ATM polymorphisms in the development of cancer. This study aims to investigate the association of two ATM single-nucleotide polymorphisms (SNPs) with lung cancer, as well as their potential interaction with p53 gene and other known risk factors of lung cancer. METHODS: A population-based case-control study was conducted in Taiyuan city, China with 399 cases and 466 controls matched on the distribution of age and sex of cases...
2017: Frontiers in Public Health
https://www.readbyqxmd.com/read/28635423/inner-retinal-dystrophy-in-a-patient-with-biallelic-sequence-variants-in-brat1
#4
Julius T Oatts, Jacque L Duncan, Creig S Hoyt, Anne M Slavotinek, Anthony T Moore
BACKGROUND: Mutations in the BRCA1-associated protein required for the ataxia telangiectasia mutated (ATM) activation-1 (BRAT1) gene cause lethal neonatal rigidity and multifocal seizure syndrome characterized by rigidity and intractable seizures and a milder phenotype with intellectual disability, seizures, nonprogressive cerebellar ataxia or dyspraxia, and cerebellar atrophy. To date, nystagmus, cortical visual impairment, impairment of central vision, optic nerve hypoplasia, and optic atrophy have been described in this condition...
March 2, 2017: Ophthalmic Genetics
https://www.readbyqxmd.com/read/28634159/a-role-for-the-nonsense-mediated-mrna-decay-pathway-in-maintaining-genome-stability-in-caenorhabditis-elegans
#5
Víctor González-Huici, Bin Wang, Anton Gartner
Ionizing radiation (IR) is commonly used in cancer therapy and is a main source of DNA double-strand-breaks (DSBs), one of the most toxic forms of DNA damage. We have used Caenorhabditis elegans as an invertebrate model to identify novel factors required for repair of DNA damage inflicted by IR. We have performed an unbiased genetic screen, finding that smg-1 mutations confer strong hypersensitivity to IR. SMG-1 is a phosphoinositide-3 kinase (PI3K) kinase involved in mediating nonsense-mediated mRNA decay (NMD) of transcripts containing premature stop codons and related to the ATM and ATR kinases which are at the apex of DNA damage signalling pathways...
June 20, 2017: Genetics
https://www.readbyqxmd.com/read/28628639/small-molecule-inhibitors-uncover-synthetic-genetic-interactions-of-human-flap-endonuclease-1-fen1-with-dna-damage-response-genes
#6
Thomas A Ward, Peter J McHugh, Stephen T Durant
Flap endonuclease 1 (FEN1) is a structure selective endonuclease required for proficient DNA replication and the repair of DNA damage. Cellularly active inhibitors of this enzyme have previously been shown to induce a DNA damage response and, ultimately, cell death. High-throughput screens of human cancer cell-lines identify colorectal and gastric cell-lines with microsatellite instability (MSI) as enriched for cellular sensitivity to N-hydroxyurea series inhibitors of FEN1, but not the PARP inhibitor olaparib or other inhibitors of the DNA damage response...
2017: PloS One
https://www.readbyqxmd.com/read/28627265/atm-radiation-and-the-risk-of-second-primary-breast-cancer
#7
Jonine L Bernstein, Patrick Concannon
PURPOSE: It was first suggested more than 40 years ago that heterozygous carriers for the human autosomal recessive disorder Ataxia-Telangiectasia (A-T) might also be at increased risk for cancer. Subsequent studies have identified the responsible gene, Ataxia-Telangiectasia Mutated (ATM), characterized genetic variation at this locus in A-T and a variety of different cancers, and described the functions of the ATM protein with respect to cellular DNA damage responses. However, an overall model of how ATM contributes to cancer risk, and in particular, the role of DNA damage in this process, remains lacking...
June 19, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28624372/taming-tricky-dsbs-atm-on-duty
#8
REVIEW
Thomas Clouaire, Aline Marnef, Gaëlle Legube
Ataxia Telangiectasia Mutated (ATM) has been known for decades as the main kinase mediating the DNA Double-Strand Break Response (DDR). Extensive studies have revealed its dual role in locally promoting detection and repair of DSBs as well as in activating global DNA damage checkpoints. However, recent studies pinpoint additional unanticipated functions for ATM in modifying both the local chromatin landscape and the global chromosome organization, more particularly at persistent breaks. Given the emergence of a novel and unexpected class of DSBs prevalently arising in transcriptionally active genes and intrinsically difficult to repair, a specific role of ATM at refractory DSBs could be an important and so far overlooked feature of Ataxia Telangiectasia (A-T) a severe disorder associated with ATM mutations...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28623070/commentary-on-inherited-dna-repair-gene-mutations-in-men-with-metastatic-prostate-cancer-pritchard-cc-mateo-j-walsh-mf-de-sarkar-n-abida-w-beltran-h-garofalo-a-gulati-r-carreira-s-eeles-r-elemento-o-rubin-ma-robinson-d-lonigro-r-hussain-m-chinnaiyan-a-vinson
#9
Stephen J Freedland, William J Aronson
BACKGROUND: Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence of germline mutations in DNA-repair genes among men with localized prostate cancer who are unselected for family predisposition is insufficient to warrant routine testing, the frequency of such mutations in patients with metastatic prostate cancer has not been established. METHODS: We recruited 692 men with documented metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis...
June 13, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28619709/loss-of-fam46c-promotes-cell-survival-in-myeloma
#10
Yuan Xiao Zhu, Chang-Xin Shi, Laura A Bruins, Patrick Jedlowski, Xuewei Wang, K Martin Kortüm, Moulun Luo, Jonathan Ahmann, Esteban Braggio, A Keith Stewart
FAM46C is one of the most recurrently mutated genes in multiple myeloma (MM), however its role in disease pathogenesis has not been determined. Here we demonstrate that wild type (WT) FAM46C overexpression induces substantial cytotoxicity in MM cells. In contrast, FAM46C mutations found in MM patients abrogate this cytotoxicity, indicating a survival advantage conferred by the FAM46C mutant phenotype. WT FAM46C overexpression downregulated IRF4, CEBPB, and MYC and upregulated immunoglobulin (Ig) light chain and HSPA5/BIP Furthermore, pathway analysis suggests that enforced FAM46C expression activated the unfolded protein response (UPR) pathway and induced mitochondrial dysfunction...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28617799/p53-and-tap63-participate-in-the-recombination-dependent-pachytene-arrest-in-mouse-spermatocytes
#11
Marina Marcet-Ortega, Sarai Pacheco, Ana Martínez-Marchal, Helena Castillo, Elsa Flores, Maria Jasin, Scott Keeney, Ignasi Roig
To protect germ cells from genomic instability, surveillance mechanisms ensure meiosis occurs properly. In mammals, spermatocytes that display recombination defects experience a so-called recombination-dependent arrest at the pachytene stage, which relies on the MRE11 complex-ATM-CHK2 pathway responding to unrepaired DNA double-strand breaks (DSBs). Here, we asked if p53 family members-targets of ATM and CHK2-participate in this arrest. We bred double-mutant mice combining a mutation of a member of the p53 family (p53, TAp63, or p73) with a Trip13 mutation...
June 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28613105/rug3-is-a-negative-regulator-of-plant-responses-to-aba-in-arabidopsis-thaliana
#12
Chao Su, Jinhong Yuan, Hongtao Zhao, Yankun Zhao, Hongtao Ji, Youning Wang, Xia Li
Mitochondria is a main target of various stressors. Dysfunction of mitochondria stimulates overproduction of reactive oxygen species (ROS), which can cause oxidative damage to mitochondria and DNA. Recently, we demonstrated that RCC1/UVR8/GEF-like 3 (RUG3), a member of the Regulator of Chromatin Condensation 1 (RCC1) protein family, can directly interact with ataxia telangiectasia mutated (ATM), a key regulator of the DNA damage response (DDR), and synergistically regulates the alternative splicing of mitochondrial nad2...
June 14, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28612525/-the-role-of-dna-double-strain-damage-repairing-mechanisms-in-diabetic-atheroscolersis
#13
Li Zeng, Qun-Fang Ding, Ting-Yuan Xu, Fang Luo, Ning Ge, Shi-Tong Li
OBJECTIVES: To identify the role of DNA double-strain damage repairing pathway in the development of diabetics atherosclerosis. METHODS: Wistar male rats were randomly divided into three groups: control group (group A), balloon injury group (group B) and diabetes + balloon injury group (group C). Streptozotocin (STZ) was injected into rat abdomen to induce diabetes. After stabilizing high glucose, rats in group B and group C were both under aortic balloon injury technique and fed high lipid forage post-operatively...
March 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28607084/systems-guided-forward-genetic-screen-reveals-a-critical-role-of-the-replication-stress-response-protein-etaa1-in-t-cell-clonal-expansion
#14
Lisa A Miosge, Yovina Sontani, Aaron Chuah, Keisuke Horikawa, Tiffany A Russell, Yan Mei, Mayura V Wagle, Debbie R Howard, Anselm Enders, David C Tscharke, Christopher C Goodnow, Ian A Parish
T-cell immunity requires extremely rapid clonal proliferation of rare, antigen-specific T lymphocytes to form effector cells. Here we identify a critical role for ETAA1 in this process by surveying random germ line mutations in mice using exome sequencing and bioinformatic annotation to prioritize mutations in genes of unknown function with potential effects on the immune system, followed by breeding to homozygosity and testing for immune system phenotypes. Effector CD8(+) and CD4(+) T-cell formation following immunization, lymphocytic choriomeningitis virus (LCMV) infection, or herpes simplex virus 1 (HSV1) infection was profoundly decreased despite normal immune cell development in adult mice homozygous for two different Etaa1 mutations: an exon 2 skipping allele that deletes Gly78-Leu119, and a Cys166Stop truncating allele that eliminates most of the 877-aa protein...
June 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28607003/p21-maintains-senescent-cell-viability-under-persistent-dna-damage-response-by-restraining-jnk-and-caspase-signaling
#15
Reut Yosef, Noam Pilpel, Nurit Papismadov, Hilah Gal, Yossi Ovadya, Ezra Vadai, Stav Miller, Ziv Porat, Shifra Ben-Dor, Valery Krizhanovsky
Cellular senescence is a permanent state of cell cycle arrest that protects the organism from tumorigenesis and regulates tissue integrity upon damage and during tissue remodeling. However, accumulation of senescent cells in tissues during aging contributes to age-related pathologies. A deeper understanding of the mechanisms regulating the viability of senescent cells is therefore required. Here, we show that the CDK inhibitor p21 (CDKN1A) maintains the viability of DNA damage-induced senescent cells. Upon p21 knockdown, senescent cells acquired multiple DNA lesions that activated ataxia telangiectasia mutated (ATM) and nuclear factor (NF)-κB kinase, leading to decreased cell survival...
June 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28607002/atm-wip1-activities-at-chromatin-control-plk1-re-activation-to-determine-g2-checkpoint-duration
#16
Himjyot Jaiswal, Jan Benada, Erik Müllers, Karen Akopyan, Kamila Burdova, Tobias Koolmeister, Thomas Helleday, René H Medema, Libor Macurek, Arne Lindqvist
After DNA damage, the cell cycle is arrested to avoid propagation of mutations. Arrest in G2 phase is initiated by ATM-/ATR-dependent signaling that inhibits mitosis-promoting kinases such as Plk1. At the same time, Plk1 can counteract ATR-dependent signaling and is required for eventual resumption of the cell cycle. However, what determines when Plk1 activity can resume remains unclear. Here, we use FRET-based reporters to show that a global spread of ATM activity on chromatin and phosphorylation of ATM targets including KAP1 control Plk1 re-activation...
June 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28605880/js-k-a-nitric-oxide-prodrug-induces-dna-damage-and-apoptosis-in-hbv-positive-hepatocellular-carcinoma-hepg2-2-15-cell
#17
Zhengyun Liu, Guangmin Li, Ying Gou, Dongyan Xiao, Guo Luo, Joseph E Saavedra, Jie Liu, Huan Wang
Hepatocellular carcinoma (HCC) is the most important cause of cancer-related death, and 85% of HCC is caused by chronic HBV infection, the prognosis of patients and the reduction of HBV DNA levels remain unsatisfactory. JS-K, a nitric oxide-releasing diazeniumdiolates, is effective against various tumors, but little is known on its effects on HBV positive HCC. We found that JS-K reduced the expression of HBsAg and HBeAg in HBV-positive HepG2.2.15 cells. This study aimed to further examine anti-tumor effects of JS-K on HepG2...
June 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28604764/limited-nucleotide-pools-restrict-epstein-barr-virus-mediated-b-cell-immortalization
#18
A Y Hafez, J E Messinger, K McFadden, G Fenyofalvi, C N Shepard, G M Lenzi, B Kim, M A Luftig
Activation of cellular oncogenes as well as infection with tumor viruses can promote aberrant proliferation and activation of the host DNA damage response. Epstein-Barr virus (EBV) infection of primary human B cells induces a transient period of hyper-proliferation, but many of these infected cells succumb to an ataxia telangiectasia mutated/checkpoint kinase 2 (ATM/Chk2)-mediated senescence-like growth arrest. In this study, we assessed the role of DNA replicative stress and nucleotide pool levels in limiting EBV-infected B-cell outgrowth...
June 12, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28602099/zerumbone-regulates-dna-repair-responding-to-ionizing-radiation-and-enhances-radiosensitivity-of-human-prostatic-cancer-cells
#19
Pai-Kai Chiang, Wei-Kung Tsai, Marcelo Chen, Wun-Rong Lin, Yung-Chiong Chow, Chih-Chiao Lee, Jong-Ming Hsu, Yu-Jen Chen
INTRODUCTION: Radiation therapy using ionizing radiation is widely used for the treatment of prostate cancer. The intrinsic radiation sensitivity of cancer cells could be enhanced by modulating multiple factors including the capacity to repair DNA damage, especially double-strand breaks (DSBs). We aimed to examine the effect of zerumbone on radiation sensitivity and its protective effects against ionizing radiation-induced DSB in human prostate cancer cells. MATERIALS AND METHODS: The human prostate cancer PC3 and DU145 cell lines were used...
June 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28598813/identification-of-a-novel-atm-inhibitor-with-cancer-cell-specific-radiosensitization-activity
#20
Amy J C Dohmen, Xiaohang Qiao, Anja Duursma, Ruud H Wijdeven, Cor Lieftink, Floor Hageman, Ben Morris, Pasi Halonen, Conchita Vens, Michiel W M van den Brekel, Huib Ovaa, Jacques Neefjes, Charlotte L Zuur
Treatment of advanced head and neck squamous cell carcinoma (HNSCC) is plagued by low survival and high recurrence rates, despite multimodal therapies. Presently, cisplatin or cetuximab is used in combination with radiotherapy which has resulted in minor survival benefits but increased severe toxicities relative to RT alone. This underscores the urgent need for improved tumor-specific radiosensitizers for better control with lower toxicities. In a small molecule screen targeting kinases, performed on three HNSCC cell lines, we identified GSK635416A as a novel radiosensitizer...
May 19, 2017: Oncotarget
keyword
keyword
102390
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"