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https://www.readbyqxmd.com/read/28392109/compartmentalization-of-dna-damage-response-between-heterochromatin-and-euchromatin-is-mediated-by-distinct-h2a-histone-variants
#1
Zdravko J Lorković, Chulmin Park, Malgorzata Goiser, Danhua Jiang, Marie-Therese Kurzbauer, Peter Schlögelhofer, Frédéric Berger
DNA double-strand break (DSB) repair depends on the ataxia telangiectasia mutated (ATM) kinase that phosphorylates the conserved C-terminal SQ motif present in the histone variant H2A.X [1-7]. In constitutive heterochromatin of mammals, DSB repair is delayed and relies on phosphorylation of the proteins HP1 and KAP1 by ATM [2, 8-14]. However, KAP1 is not conserved in plants and the HP1-related protein Like-HP1 (LHP1) is not localized at constitutive heterochromatin [15], suggesting that in plants, alternative mechanisms could be responsible for repair of DSBs in heterochromatin...
April 5, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28334004/the-mouse-genome-displays-highly-dynamic-populations-of-krab-zinc-finger-protein-genes-and-related-genetic-units
#2
Annamaria Kauzlaric, Gabriela Ecco, Marco Cassano, Julien Duc, Michael Imbeault, Didier Trono
KRAB-containing poly-zinc finger proteins (KZFPs) constitute the largest family of transcription factors encoded by mammalian genomes, and growing evidence indicates that they fulfill functions critical to both embryonic development and maintenance of adult homeostasis. KZFP genes underwent broad and independent waves of expansion in many higher vertebrates lineages, yet comprehensive studies of members harbored by a given species are scarce. Here we present a thorough analysis of KZFP genes and related units in the murine genome...
2017: PloS One
https://www.readbyqxmd.com/read/28327001/autophagy-promotes-the-repair-of-radiation-induced-dna-damage-in-bone-marrow-hematopoietic-cells-via-enhanced-stat3-signaling
#3
Fei Xu, Xin Li, Lili Yan, Na Yuan, Yixuan Fang, Yan Cao, Li Xu, Xiaoying Zhang, Lan Xu, Chaorong Ge, Ni An, Gaoyue Jiang, Jialing Xie, Han Zhang, Jiayi Jiang, Xiaotian Li, Lei Yao, Suping Zhang, Daohong Zhou, Jianrong Wang
Autophagy protects hematopoietic cells from radiation damage in part by promoting DNA damage repair. However, the molecular mechanisms by which autophagy regulates DNA damage repair remain largely elusive. Here, we report that this radioprotective effect of autophagy depends on STAT3 signaling in murine bone marrow mononuclear cells (BM-MNCs). Specifically, we found that STAT3 activation and nuclear translocation in BM-MNCs were increased by activation of autophagy with an mTOR inhibitor and decreased by knockout of the autophagy gene Atg7...
March 2017: Radiation Research
https://www.readbyqxmd.com/read/28263788/discovery-of-a-novel-oocyte-specific-kr%C3%A3-ppel-associated-box-domain-containing-zinc-finger-protein-required-for-early-embryogenesis-in-cattle
#4
Jacqelyn M Hand, Kun Zhang, Lei Wang, Prasanthi P Koganti, Kristen Mastrantoni, Sandeep K Rajput, Mohamed Ashry, George W Smith, Jianbo Yao
Zinc finger (ZNF) transcription factors interact with DNA through zinc finger motifs and play important roles in a variety of cellular functions including cell growth, proliferation, development, apoptosis, and intracellular signal transduction. One-third of ZNF proteins in metazoans contain a highly conserved N-terminal motif known as the Krüppel-associated box (KRAB) domain, which acts as a potent, DNA-binding dependent transcriptional repression module. Analysis of RNA-Seq data generated from a bovine oocyte cDNA library identified a novel transcript, which encodes a KRAB-containing ZNF transcription factor (named ZNFO)...
March 2, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28249048/chloroquine-triggers-epstein-barr-virus-replication-through-phosphorylation-of-kap1-trim28-in-burkitt-lymphoma-cells
#5
Xiaofan Li, Eric M Burton, Sumita Bhaduri-McIntosh
Trials to reintroduce chloroquine into regions of Africa where P. falciparum has regained susceptibility to chloroquine are underway. However, there are long-standing concerns about whether chloroquine increases lytic-replication of Epstein-Barr virus (EBV), thereby contributing to the development of endemic Burkitt lymphoma. We report that chloroquine indeed drives EBV replication by linking the DNA repair machinery to chromatin remodeling-mediated transcriptional repression. Specifically, chloroquine utilizes ataxia telangiectasia mutated (ATM) to phosphorylate the universal transcriptional corepressor Krüppel-associated Box-associated protein 1/tripartite motif-containing protein 28 (KAP1/TRIM28) at serine 824 -a mechanism that typically facilitates repair of double-strand breaks in heterochromatin, to instead activate EBV...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28236007/function-of-heterochromatin-protein-1-during-dna-repair
#6
REVIEW
Eva Bártová, Barbora Malyšková, Denisa Komůrková, Soňa Legartová, Jana Suchánková, Jana Krejčí, Stanislav Kozubek
This review focuses on the function of heterochromatin protein HP1 in response to DNA damage. We specifically outline the regulatory mechanisms in which HP1 and its interacting partners are involved. HP1 protein subtypes (HP1α, HP1β, and HP1γ) are the main components of constitutive heterochromatin, and HP1α and HP1β in particular are responsible for heterochromatin maintenance. The recruitment of these proteins to DNA lesions is also important from the perspective of proper DNA repair mechanisms. For example, HP1α is necessary for the binding of the main DNA damage-related protein 53BP1 at DNA repair foci, which are positive not only for the HP1α protein but also for the RAD51 protein, a component of DNA repair machinery...
May 2017: Protoplasma
https://www.readbyqxmd.com/read/28215224/the-complex-role-of-the-znf224-transcription-factor-in-cancer
#7
E Cesaro, G Sodaro, G Montano, M Grosso, A Lupo, P Costanzo
ZNF224 is a member of the Kruppel-associated box zinc finger proteins (KRAB-ZFPs) family. It was originally identified as a transcriptional repressor involved in gene-specific silencing through the recruitment of the corepressor KAP1, chromatin-modifying activities, and the arginine methyltransferase PRMT5 on the promoter of its target genes. Recent findings indicate that ZNF224 can behave both as a tumor suppressor or an oncogene in different human cancers. The transcriptional regulatory properties of ZNF224 in these systems appear to be complex and influenced by specific sets of interactors...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28178212/anti-inflammatory-activity-of-sanghuangporus-sanghuang-mycelium
#8
Wang-Ching Lin, Jeng-Shyan Deng, Shyh-Shyun Huang, Sheng-Hua Wu, Chin-Chu Chen, Wan-Rong Lin, Hui-Yi Lin, Guan-Jhong Huang
Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with lipopolysaccharides (LPS)-induced ALI in mice and to investigate its possible mechanism of action...
February 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28134929/the-evolutionary-capacitor-hsp90-buffers-the-regulatory-effects-of-mammalian-endogenous-retroviruses
#9
Barbara Hummel, Erik C Hansen, Aneliya Yoveva, Fernando Aprile-Garcia, Rebecca Hussong, Ritwick Sawarkar
Understanding how genotypes are linked to phenotypes is important in biomedical and evolutionary studies. The chaperone heat-shock protein 90 (HSP90) buffers genetic variation by stabilizing proteins with variant sequences, thereby uncoupling phenotypes from genotypes. Here we report an unexpected role of HSP90 in buffering cis-regulatory variation affecting gene expression. By using the tripartite-motif-containing 28 (TRIM28; also known as KAP1)-mediated epigenetic pathway, HSP90 represses the regulatory influence of endogenous retroviruses (ERVs) on neighboring genes that are critical for mouse development...
March 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27898713/peg3-interacts-with-kap1-through-krab-a
#10
Hongzhi He, An Ye, Hana Kim, Joomyeong Kim
Peg3 (Paternally Expressed Gene 3) is an imprinted gene that encodes a zinc finger DNA-binding protein. Peg3 itself is localized in the middle of a KRAB-A (Kruppel-Associated Box) zinc finger gene cluster. The amino acid sequence encoded by its exon 7 also shows sequence similarity to that of KRAB-A, suggesting Peg3 as a KRAB-containing zinc finger gene. As predicted, the PEG3 protein was co-immunoprecipitated with KAP1, a co-repressor that interacts with KRAB-A. A series of follow-up experiments further demonstrated that the exon 7 of PEG3 is indeed responsible for its physical interaction with KAP1...
2016: PloS One
https://www.readbyqxmd.com/read/27867147/evolution-of-krab-containing-zinc-finger-proteins-and-their-roles-in-species-evolution
#11
Wang Jinlong, Wang Jian, Tian Chunyan
The C2H2 zinc finger protein family, one of the largest families of transcription factor/transcriptional regulator in mammal, arose from a small ancestral group of eukaryotic zinc finger transcription factors through many repeated gene duplications accompanied by functional divergence. As the biggest subfamily of C2H2 zinc finger protein family, Kruppel-associated box-containing zinc finger proteins (KRAB-ZFPs) appeared at the period oftetrapod, expand rapidly along with species evolution, and take about 60% of the total C2H2 zinc finger proteins in human...
November 20, 2016: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/27845900/trim28-multi-domain-protein-regulates-cancer-stem-cell-population-in-breast-tumor-development
#12
Patrycja Czerwińska, Parantu K Shah, Katarzyna Tomczak, Marta Klimczak, Sylwia Mazurek, Barbara Sozańska, Przemysław Biecek, Konstanty Korski, Violetta Filas, Andrzej Mackiewicz, Jannik N Andersen, Maciej Wiznerowicz
The expression of Tripartite motif-containing protein 28 (TRIM28)/Krüppel-associated box (KRAB)-associated protein 1 (KAP1), is elevated in at least 14 tumor types, including solid and hematopoietic tumors. High level of TRIM28 is associated with triple-negative subtype of breast cancer (TNBC), which shows higher aggressiveness and lower survival rates. Interestingly, TRIM28 is essential for maintaining the pluripotent phenotype in embryonic stem cells. Following on that finding, we evaluated the role of TRIM28 protein in the regulation of breast cancer stem cells (CSC) populations and tumorigenesis in vitro and in vivo...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27795446/transcriptional-silencing-of-moloney-murine-leukemia-virus-in-human-embryonic-carcinoma-cells
#13
Gary Z Wang, Stephen P Goff
Embryonic carcinoma (EC) cells are malignant counterparts of embryonic stem (ES) cells and serve as useful models for investigating cellular differentiation and human embryogenesis. Though the susceptibility of murine EC cells to retroviral infection has been extensively analyzed, few studies of retrovirus infection of human EC cells have been performed. We tested the susceptibility of human EC cells to transduction by retroviral vectors derived from three different retroviral genera. We show that human EC cells efficiently express reporter genes delivered by vectors based on human immunodeficiency virus type 1 (HIV-1) and Mason-Pfizer monkey virus (M-PMV) but not Moloney murine leukemia virus (MLV)...
January 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27780869/uri-regulates-kap1-phosphorylation-and-transcriptional-repression-via-pp2a-phosphatase-in-prostate-cancer-cells
#14
Paolo Mita, Jeffrey N Savas, Erica M Briggs, Susan Ha, Veena Gnanakkan, John R Yates, Diane M Robins, Gregory David, Jef D Boeke, Michael J Garabedian, Susan K Logan
URI (unconventional prefoldin RPB5 interactor protein) is an unconventional prefoldin, RNA polymerase II interactor that functions as a transcriptional repressor and is part of a larger nuclear protein complex. The components of this complex and the mechanism of transcriptional repression have not been characterized. Here we show that KAP1 (KRAB-associated protein 1) and the protein phosphatase PP2A interact with URI. Mechanistically, we show that KAP1 phosphorylation is decreased following recruitment of PP2A by URI...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27601472/o-glcnacase-is-an-rna-polymerase-ii-elongation-factor-coupled-to-pausing-factors-spt5-and-tif1%C3%AE
#15
Melissa Resto, Bong-Hyun Kim, Alfonso G Fernandez, Brian J Abraham, Keji Zhao, Brian A Lewis
We describe here the identification and functional characterization of the enzyme O-GlcNAcase (OGA) as an RNA polymerase II elongation factor. Using in vitro transcription elongation assays, we show that OGA activity is required for elongation in a crude nuclear extract system, whereas in a purified system devoid of OGA the addition of rOGA inhibited elongation. Furthermore, OGA is physically associated with the known RNA polymerase II (pol II) pausing/elongation factors SPT5 and TRIM28-KAP1-TIF1β, and a purified OGA-SPT5-TIF1β complex has elongation properties...
October 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27588518/atm-function-and-its-relationship-with-atm-gene-mutations-in-chronic-lymphocytic-leukemia-with-the-recurrent-deletion-11q22-3-23-2
#16
Y Jiang, H-C Chen, X Su, P A Thompson, X Liu, K-A Do, W Wierda, M J Keating, W Plunkett
Approximately 10-20% of chronic lymphocytic leukemia (CLL) patients exhibit del(11q22-23) before treatment, this cohort increases to over 40% upon progression following chemoimmunotherapy. The coding sequence of the DNA damage response gene, ataxia-telangiectasia-mutated (ATM), is contained in this deletion. The residual ATM allele is frequently mutated, suggesting a relationship between gene function and clinical response. To investigate this possibility, we sought to develop and validate an assay for the function of ATM protein in these patients...
September 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27364555/metabolic-stress-induced-phosphorylation-of-kap1-ser473-blocks-mitochondrial-fusion-in-breast-cancer-cells
#17
Chun-Ting Cheng, Ching-Ying Kuo, Ching Ouyang, Chien-Feng Li, Yiyin Chung, David C Chan, Hsing-Jien Kung, David K Ann
Mitochondrial dynamics during nutrient starvation of cancer cells likely exert profound effects on their capability for metastatic progression. Here, we report that KAP1 (TRIM28), a transcriptional coadaptor protein implicated in metastatic progression in breast cancer, is a pivotal regulator of mitochondrial fusion in glucose-starved cancer cells. Diverse metabolic stresses induced Ser473 phosphorylation of KAP1 (pS473-KAP1) in a ROS- and p38-dependent manner. Results from live-cell imaging and molecular studies revealed that during the first 6 to 8 hours of glucose starvation, mitochondria initially underwent extensive fusion, but then subsequently fragmented in a pS473-KAP1-dependent manner...
September 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27271602/v-src-causes-chromosome-bridges-in-a-caffeine-sensitive-manner-by-generating-dna-damage
#18
Masayoshi Ikeuchi, Yasunori Fukumoto, Takuya Honda, Takahisa Kuga, Youhei Saito, Naoto Yamaguchi, Yuji Nakayama
An increase in Src activity is commonly observed in epithelial cancers. Aberrant activation of the kinase activity is associated with malignant progression. However, the mechanisms that underlie the Src-induced malignant progression of cancer are not completely understood. We show here that v-Src, an oncogene that was first identified from a Rous sarcoma virus and a mutant variant of c-Src, leads to an increase in the number of anaphase and telophase cells having chromosome bridges. v-Src increases the number of γH2AX foci, and this increase is inhibited by treatment with PP2, a Src kinase inhibitor...
June 2, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27199493/ultrastructural-insights-into-the-biological-significance-of-persisting-dna-damage-foci-after-low-doses-of-ionizing-radiation
#19
Yvonne Lorat, Stefanie Schanz, Claudia E Ruebe
PURPOSE: Intensity-modulated radiotherapy (IMRT) enables the delivery of high doses to target volume while sparing surrounding non-targeted tissues. IMRT treatment, however, substantially increases the normal-tissue volume receiving low-dose irradiation, but the biological consequences are unclear. EXPERIMENTAL DESIGN: Using mouse strains that varied in genetic DNA repair capacity, we investigated the DNA damage response of cortical neurons during daily low-dose irradiation (0...
May 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27185882/nitric-oxide-suppresses-%C3%AE-cell-apoptosis-by-inhibiting-the-dna-damage-response
#20
Bryndon J Oleson, Katarzyna A Broniowska, Aaron Naatz, Neil Hogg, Vera L Tarakanova, John A Corbett
Nitric oxide, produced in pancreatic β cells in response to proinflammatory cytokines, plays a dual role in the regulation of β-cell fate. While nitric oxide induces cellular damage and impairs β-cell function, it also promotes β-cell survival through activation of protective pathways that promote β-cell recovery. In this study, we identify a novel mechanism in which nitric oxide prevents β-cell apoptosis by attenuating the DNA damage response (DDR). Nitric oxide suppresses activation of the DDR (as measured by γH2AX formation and the phosphorylation of KAP1 and p53) in response to multiple genotoxic agents, including camptothecin, H2O2, and nitric oxide itself, despite the presence of DNA damage...
August 1, 2016: Molecular and Cellular Biology
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