keyword
MENU ▼
Read by QxMD icon Read
search

Rad50

keyword
https://www.readbyqxmd.com/read/28324505/probing-the-telomere-damage-response
#1
Rekha Rai, Sandy Chang
Telomere dysfunctions, rendered through replicative attrition of telomeric DNA or due to the removal of shelterin components, are recognized as DNA double-stranded breaks (DSBs) by the DNA damage repair (DDR) pathway. This leads to the activation of DNA damage checkpoint sensors, including the Mre11-Rad50-Nbs1 (MRN) complex, γ-H2AX and 53BP1, the ATM and ATR signal-transducing kinases, and downstream effectors, including Chk1, Chk2, and p53. Robust DNA damage response signals at dysfunctional telomeres, achieved by the complete deletion of TRF2 or by expressing dominant-negative mutant TPP1ΔRD, can be detected by their association with γ-H2AX and 53BP1 forming "telomere dysfunction induced foci (TIFs)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28292918/non-homologous-end-joining-with-minimal-sequence-loss-is-promoted-by-the-mre11-rad50-nbs1-ctp1-complex-in-schizosaccharomyces-pombe
#2
Yanhui Li, Jinyu Wang, Gang Zhou, Michael Lajeunesse, Nga Le, Brittany N Stawicki, Yalitza Lopez Corcino, Kathleen L Berkner, Kurt W Runge
While the Mre11-Rad50-Nbs1 (MRN) complex has known roles in repair processes like homologous recombination and microhomology-mediated end-joining, its role in non-homologous end-joining (NHEJ) is unclear as Saccharomyces cerevisiae, Schizosaccharomyces pombe and mammals have different requirements for repairing cut DNA ends. Most double-strand breaks (DSBs) require nucleolytic processing prior to DNA ligation. We therefore studied repair using the Hermes transposon, whose excision leaves a DSB capped by hairpin ends similar to structures generated by palindromes and trinucleotide repeats...
March 14, 2017: Genetics
https://www.readbyqxmd.com/read/28264000/evaluation-of-rint1-as-a-modifier-of-intestinal-tumorigenesis-and-cancer-risk
#3
Karla L Otterpohl, Karen A Gould
The Rad50 Interacting Protein 1 (Rint1) influences cellular homeostasis through maintenance of endoplasmic reticulum, Golgi and centrosome integrity and regulation of vesicle transport, autophagy and the G2/M checkpoint. Rint1 has been postulated to function as a tumor suppressor as well as an oncogene, with its role depending perhaps upon the precise cellular and/or experimental context. In humans, heterozygosity for germline missense variants in RINT1 have, in some studies, been associated with increased risk of both breast and Lynch syndrome type cancers...
2017: PloS One
https://www.readbyqxmd.com/read/28261280/effect-of-irradiation-on-dna-synthesis-nbn-gene-expression-and-chromosomal-stability-in-cells-with-nbn-mutations
#4
Jerzy Nowak, Bogna Świątek-Kościelna, Ewelina M Kałużna, Jolanta Rembowska, Agnieszka Dzikiewicz-Krawczyk, Mariola Zawada, Danuta Januszkiewicz-Lewandowska
INTRODUCTION: The NBN gene product is part of the MRE11/RAD50/NBN complex, which plays an essential role in genomic stability. In the study we try to answer the question what is the effect of irradiation on DNA synthesis, NBN gene expression and chromosomal stability in cells with homozygous c.657-661del, and heterozygous c.657-661del, p.I171V and p.R215W NBN gene mutations. MATERIAL AND METHODS: Immortalized B-lymphocytes with NBN gene mutations were X-ray irradiated at doses of 1, 2, 5 and 8 Gy/min...
March 1, 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28241424/exome-sequencing-in-a-family-with-luminal-type-breast-cancer-underpinned-by-variation-in-the-methylation-pathway
#5
Nicole van der Merwe, Armand V Peeters, Fredrieka M Pienaar, Juanita Bezuidenhout, Susan J van Rensburg, Maritha J Kotze
Panel-based next generation sequencing (NGS) is currently preferred over whole exome sequencing (WES) for diagnosis of familial breast cancer, due to interpretation challenges caused by variants of uncertain clinical significance (VUS). There is also no consensus on the selection criteria for WES. In this study, a pathology-supported genetic testing (PSGT) approach was used to select two BRCA1/2 mutation-negative breast cancer patients from the same family for WES. Homozygosity for the MTHFR 677 C>T mutation detected during this PSGT pre-screen step was considered insufficient to cause bilateral breast cancer in the index case and her daughter diagnosed with early-onset breast cancer (<30 years)...
February 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28217912/cold-adaptation-of-the-antarctic-haloarchaea-halohasta-litchfieldiae-and-halorubrum-lacusprofundi
#6
Timothy J Williams, Yan Liao, Jun Ye, Rhiannon P Kuchel, Anne Poljak, Mark J Raftery, Ricardo Cavicchioli
Halohasta litchfieldiae represents ∼ 44% and Halorubrum lacusprofundi ∼ 10% of the hypersaline, perennially cold (≥ -20°C) Deep Lake community in Antarctica. We used proteomics and microscopy to define physiological responses of these haloarchaea to growth at high (30°C) and low (10 and 4°C) temperatures. The proteomic data indicate that both species responded to low temperature by modifying their cell envelope including protein N-glycosylation, maintaining osmotic balance and translation initiation, and modifying RNA turnover and tRNA modification...
February 20, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28216226/nbs1-phosphorylation-status-dictates-repair-choice-of-dysfunctional-telomeres
#7
Rekha Rai, Chunyi Hu, Cayla Broton, Yong Chen, Ming Lei, Sandy Chang
Telomeres employ TRF2 to protect chromosome ends from activating the DNA damage sensor MRE11-RAD50-NBS1 (MRN), thereby repressing ATM-dependent DNA damage checkpoint responses. How TRF2 prevents MRN activation at dysfunctional telomeres is unclear. Here, we show that the phosphorylation status of NBS1 determines the repair pathway choice of dysfunctional telomeres. The crystal structure of the TRF2-NBS1 complex at 3.0 Å resolution shows that the NBS1 429YQLSP433 motif interacts specifically with the TRF2(TRFH) domain...
February 8, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28195137/erbb4-confers-risk-for-polycystic-ovary-syndrome-in-han-chinese
#8
Yingqian Peng, Wei Zhang, Ping Yang, Ye Tian, Shizhen Su, Changming Zhang, Zi-Jiang Chen, Han Zhao
A recent genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in European cohorts has identified six susceptibility loci mapping to 11q22.1 (YAP1), 2p21 (THADA), 11p14.1 (FSHB), 2q34 (ERBB4), 12q21.2 (KRR1), and 5q31.1 (RAD50). The loci of 11q22.1, 2p21 and 11p14.1 have been confirmed to be associated with PCOS in Chinese; whereas the other three new loci (2q34, 12q21.2, and 5q31.1) still need to be evaluated in Chinese. This study was aimed to determine if the three new loci identified in European PCOS also confer risks for PCOS in Han Chinese...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28178675/overexpression-of-karyopherin-a2-in-cholangiocarcinoma-correlates-with-poor-prognosis-and-gemcitabine-sensitivity-via-nuclear-translocation-of-dna-repair-proteins
#9
Mariko Tsukagoshi, Kenichiro Araki, Takehiko Yokobori, Bolag Altan, Hideki Suzuki, Norio Kubo, Akira Watanabe, Norihiro Ishii, Yasuo Hosouchi, Masahiko Nishiyama, Ken Shirabe, Hiroyuki Kuwano
Cholangiocarcinoma is a highly malignant tumor, and the development of new therapeutic strategies is critical. Karyopherin-α2 (KPNA2) functions as an adaptor that mediates nucleocytoplasmic transport. Specifically, KPNA2 transports one of the important DNA repair machineries, the MRE11-RAD50-NBS1 (MRN) complex, to the nucleus. In this study, we clarified the significance of KPNA2 in cholangiocarcinoma. KPNA2 expression evaluated by immunohistochemical analysis was common in malignant tissue but rare in adjacent noncancerous tissues...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28137761/comprehensive-transcriptome-and-mutational-profiling-of-endemic-burkitt-lymphoma-reveals-ebv-type-specific-differences
#10
Yasin Kaymaz, Cliff I Oduor, Hongbo Yu, Juliana A Otieno, John M Ong'echa, Ann M Moormann, Jeffrey A Bailey
Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in malaria-endemic equatorial Africa and nearly always contains Epstein-Barr virus (EBV), unlike sporadic Burkitt Lymphoma (sBL) that occurs with a lower incidence in developed countries. Given these differences and the variable clinical presentation and outcomes, we sought to further understand pathogenesis by investigating transcriptomes using RNA sequencing (RNAseq) from multiple primary eBL tumors compared to sBL tumors. Within eBL tumors, minimal expression differences were found based on: anatomical presentation site, in-hospital survival rates, and EBV genome type; suggesting that eBL tumors are homogeneous without marked subtypes...
January 30, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28134932/eukaryotic-rad50-functions-as-a-rod-shaped-dimer
#11
Young Bong Park, Marcel Hohl, Michał Padjasek, Eunyoung Jeong, Kyeong Sik Jin, Artur Krężel, John H J Petrini, Yunje Cho
The Rad50 hook interface is crucial for assembly and various functions of the Mre11 complex. Previous analyses suggested that Rad50 molecules interact within (intracomplex) or between (intercomplex) dimeric complexes. In this study, we determined the structure of the human Rad50 hook and coiled-coil domains. The data suggest that the predominant structure is the intracomplex, in which the two parallel coiled coils proximal to the hook form a rod shape, and that a novel interface within the coiled-coil domains of Rad50 stabilizes the interaction of Rad50 protomers in the dimeric assembly...
January 30, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28132936/rhs6-mediated-chromosomal-looping-and-nuclear-substructure-binding-is-required-for-th2-cytokine-gene-expression
#12
Soo Seok Hwang, Sung Woong Jang, Gap Ryol Lee
Subset-specific gene expression is a critical feature of CD4 T cell differentiation. Th2 cells express Th2 cytokine genes including Il4, Il5, and Il13 and mediate the immune response against helminths. The expression of Th2 cytokine genes is regulated by Rad50 hypersensitive site 6 (RHS6) in the Th2 locus control region; however, the molecular mechanisms of RHS6 action at the chromatin level are poorly understood. Here, we demonstrate that RHS6 is crucial for chromosomal interactions and nuclear substructure binding of the Th2 cytokine locus...
March 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28128338/interplay-with-the-mre11-rad50-nbs1-complex-and-phosphorylation-by-gsk3%C3%AE-implicate-human-b-myb-in-dna-damage-signaling
#13
Sarah Marie Henrich, Clemens Usadel, Eugen Werwein, Kamila Burdova, Pavel Janscak, Stefano Ferrari, Daniel Hess, Karl-Heinz Klempnauer
B-Myb, a highly conserved member of the Myb transcription factor family, is expressed ubiquitously in proliferating cells and controls the cell cycle dependent transcription of G2/M-phase genes. Deregulation of B-Myb has been implicated in oncogenesis and loss of genomic stability. We have identified B-Myb as a novel interaction partner of the Mre11-Rad50-Nbs1 (MRN) complex, a key player in the repair of DNA double strand breaks. We show that B-Myb directly interacts with the Nbs1 subunit of the MRN complex and is recruited transiently to DNA-damage sites...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28108985/the-th2-gene-cluster-unraveled-role-of-rhs6
#14
EDITORIAL
Cameron H Flayer, Angela Haczku
Although the transcription factors that regulate T helper (Th) type 2 cytokine production (IL-4, IL-5, and IL-13) are possible novel therapeutic targets, we lack a detailed understanding of the mechanisms that regulate the transcription of these cytokines. In this issue of Allergy, Hwang et al. studied the role of a specific DNA region (a cis-acting element called Rad50 hypersensitive site 6) RHS6, in the development of allergic airway inflammation. RHS6 is found in the Th2 cytokine "locus control region" but its role in activation of the IL-4, IL-5, and IL-13 genes was unknown...
January 20, 2017: Allergy
https://www.readbyqxmd.com/read/28102005/blind-prediction-of-deleterious-amino-acid-variations-with-snps-go
#15
Emidio Capriotti, Pier Luigi Martelli, Piero Fariselli, Rita Casadio
SNPs&GO is a machine learning method for predicting the association of single amino acid variations (SAVs) to disease, considering protein functional annotation. The method is a binary classifier that implements a Support Vector Machine algorithm to discriminate between disease-related and neutral SAVs. SNPs&GO combines information from protein sequence with functional annotation encoded by Gene Ontology terms. Tested in sequence mode on more than 38,000 SAVs from the SwissVar dataset, our method reached 81% overall accuracy and an area under the receiving operating characteristic curve (AUC) of 0...
January 19, 2017: Human Mutation
https://www.readbyqxmd.com/read/28076792/the-mre11-nbs1-interface-is-essential-for-viability-and-tumor-suppression
#16
Jun Hyun Kim, Malgorzata Grosbart, Roopesh Anand, Claire Wyman, Petr Cejka, John H J Petrini
The Mre11 complex (Mre11, Rad50, and Nbs1) is integral to both DNA repair and ataxia telangiectasia mutated (ATM)-dependent DNA damage signaling. All three Mre11 complex components are essential for viability at the cellular and organismal levels. To delineate essential and non-essential Mre11 complex functions that are mediated by Nbs1, we used TALEN-based genome editing to derive Nbs1 mutant mice (Nbs1(mid) mice), which harbor mutations in the Mre11 interaction domain of Nbs1. Nbs1(mid) alleles that abolished interaction were incompatible with viability...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28073364/lack-of-mre11-rad50-nbs1-mrn-complex-detection-occurs-frequently-in-low-grade-epithelial-ovarian-cancer
#17
Simone Brandt, Eleftherios P Samartzis, Anne-Katrin Zimmermann, Daniel Fink, Holger Moch, Aurelia Noske, Konstantin J Dedes
BACKGROUND: BRCA1/2-deficient ovarian carcinomas are recognized as target for Poly (ADP-ribose) polymerase (PARP) inhibitors. BRCA1 and BRCA2 proteins are involved in homologous recombination repair of double-strand DNA breaks. The relevance of other homologous recombination repair proteins, e.g. MRE11, RAD50, NBS1 (MRN complex) in ovarian carcinomas is unclear. The objective of this study was to investigate the prevalence of lack of MRE11, RAD50, NBS1 protein detection in epithelial ovarian cancer (EOC)...
January 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28031358/association-of-human-papillomavirus-16-e2-with-rad50-interacting-protein-1-enhances-viral-dna-replication
#18
Karen Campos-León, Kalpanee Wijendra, Abida Siddiqa, Ieisha Pentland, Katherine M Feeney, Alison Knapman, Rachel Davies, Elliot J Androphy, Joanna L Parish
Rad50-interacting protein 1 (Rint1) associates with the DNA damage response protein Rad50 during the transition from the S phase to the G2/M phase and functions in radiation-induced G2 checkpoint control. It has also been demonstrated that Rint1 is essential in vesicle trafficking from the Golgi apparatus to the endoplasmic reticulum (ER) through an interaction with Zeste-White 10 (ZW10). We have isolated a novel interaction between Rint1 and the human papillomavirus 16 (HPV16) transcription and replication factor E2...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27997699/chromatin-remodelling-and-dna-repair-genes-are-frequently-mutated-in-endometrioid-endometrial-carcinoma
#19
Pablo García-Sanz, Juan Carlos Triviño, Alba Mota, María Pérez López, Eva Colás, Alejandro Rojo-Sebastián, Ángel García, Sonia Gatius, María Ruiz, Jaime Prat, Rafael López-López, Miguel Abal, Antonio Gil-Moreno, Jaume Reventós, Xavier Matias-Guiu, Gema Moreno-Bueno
In developed countries, endometrial carcinoma is the most common cancer that affects the female genital tract. Endometrial carcinoma is divided into two main histological types, type I or endometrioid and type II or non-endometrioid, each of which have characteristic, although not exclusive, molecular alterations and mutational profiles. Nevertheless, information about the implication and relevance of some of these genes in this disease is lacking. We sought here to identify new recurrently mutated genes in endometrioid cancers that play a role in tumourigenesis and that influence the clinical outcome...
April 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27966484/genetic-and-biochemical-evidences-reveal-novel-insights-into-the-mechanism-underlying-saccharomyces-cerevisiae-sae2-mediated-abrogation-of-dna-replication-stress
#20
Indrajeet Ghodke, K Muniyappa
In Saccharomyces cerevisiae, the Mre11-Rad50-Xrs2 (MRX) protein complex plays pivotal roles in double-strand break (DSB) repair, replication stress and telomere length maintenance. Another protein linked to DSB repair is Sae2, which regulates MRX persistence at DSBs. However, very little is known about its role in DNA replication stress and repair. Here, we reveal a crucial role for Sae2 in DNA replication stress. We show that different mutant alleles of SAE2 cause hypersensitivity to genotoxic agents, and when combined with Δmre11 or nuclease-defective mre11 mutant alleles, the double mutants are considerably more sensitive suggesting that the sae2 mutations synergize with mre11 mutations...
December 2016: Journal of Biosciences
keyword
keyword
12756
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"