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https://www.readbyqxmd.com/read/28528517/loss-of-msh2-and-msh6-due-to-heterozygous-germline-defects-in-msh3-and-msh6
#1
Monika Morak, Sarah Käsbauer, Martina Kerscher, Andreas Laner, Anke M Nissen, Anna Benet-Pagès, Hans K Schackert, Gisela Keller, Trisari Massdorf, Elke Holinski-Feder
Lynch Syndrome (LS) is the most common dominantly inherited colorectal cancer (CRC) predisposition and is caused by a heterozygous germline defect in one of the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2. High microsatellite instability (MSI-H) and loss of MMR protein expression in tumours reflecting a defective MMR are indicators for LS, as well as a positive family history of early onset CRC. MSH2 and MSH6 form a major functional heterodimer, and MSH3 is an alternative binding partner for MSH2...
May 20, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28528442/herpesvirus-capsid-assembly-and-dna-packaging
#2
Jason D Heming, James F Conway, Fred L Homa
Herpes simplex virus type I (HSV-1) is the causative agent of several pathologies ranging in severity from the common cold sore to life-threatening encephalitic infection. During productive lytic infection, over 80 viral proteins are expressed in a highly regulated manner, resulting in the replication of viral genomes and assembly of progeny virions. The virion of all herpesviruses consists of an external membrane envelope, a proteinaceous layer called the tegument, and an icosahedral capsid containing the double-stranded linear DNA genome...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28527797/mir-26b-promoter-analysis-reveals-regulatory-mechanisms-by-lipid-related-transcription-factors-in-goat-mammary-epithelial-cells
#3
Hui Wang, Jun Luo, Qiuya He, Dawei Yao, Jiao Wu, Juan J Loor
MicroRNA (miRNA) regulate protein abundance and control diverse aspects of cellular processes and biological functions associated with lipid metabolism. MiR-26b and its host gene CTDSP1 regulate triacylglycerol synthesis by synergistically suppressing the insulin-induced gene 1 (INSIG1); however, the direct regulators of miR-26b expression remain unknown. In the present study, we characterized the activity of a novel putative promoter region in miR-26b. Results revealed that promoter activity and miR-26b expression are dynamically regulated by different transcription factors including peroxisome proliferator-activated receptor gamma (PPARG), sterol regulatory element binding transcription factor 1 (SREBF1), and liver X receptor α (LXRα)...
May 17, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28527011/the-prdm9-krab-domain-is-required-for-meiosis-and-involved-in-protein-interactions
#4
Yukiko Imai, Frédéric Baudat, Miguel Taillepierre, Marcello Stanzione, Attila Toth, Bernard de Massy
PR domain-containing protein 9 (PRDM9) is a major regulator of the localization of meiotic recombination hotspots in the human and mouse genomes. This role involves its DNA-binding domain, which is composed of a tandem array of zinc fingers, and PRDM9-dependent trimethylation of histone H3 at lysine 4. PRDM9 is a member of the PRDM family of transcription regulators, but unlike other family members, it contains a Krüppel-associated box (KRAB)-related domain that is predicted to be a potential protein interaction domain...
May 19, 2017: Chromosoma
https://www.readbyqxmd.com/read/28526714/constans-imparts-dna-sequence-specificity-to-the-histone-fold-nf-yb-nf-yc-dimer
#5
Nerina Gnesutta, Roderick W Kumimoto, Swadhin Swain, Matteo Chiara, Chamindika Siriwardana, David Stephen Horner, Ben F Holt, Roberto Mantovani
NF-Y is a heterotrimeric transcription factor that binds CCAAT elements. The NF-Y trimer is composed of a Histone Fold Domain (HFD) dimer (NF-YB/NF-YC) and NF-YA, which confers DNA sequence-specificity. NF-YA shares a conserved domain with the CCT (CONSTANS, CONSTANS-LIKE, TOC1) proteins. We show that CONSTANS (CO/BBX1), a master flowering regulator, forms a trimer with Arabidopsis NF-YB2/NF-YC3 to efficiently bind the CORE element of the FT promoter. We term this complex NF-CO. Using saturation mutagenesis EMSAs and RNA-Seq profiling of co, nf-yb, and nf-yc mutants, we identify CCACA elements as the core NF-CO binding site...
May 19, 2017: Plant Cell
https://www.readbyqxmd.com/read/28526090/reduced-hdac2-in-skeletal-muscle-of-copd-patients
#6
Masako To, Elisabeth B Swallow, Kenich Akashi, Kosuke Haruki, S Amanda Natanek, Michael I Polkey, Kazuhiro Ito, Peter J Barnes
BACKGROUND: Skeletal muscle weakness in chronic obstructive pulmonary disease (COPD) is an important predictor of poor prognosis, but the molecular mechanisms of muscle weakness in COPD have not been fully elucidated. The aim of this study was to investigate the role of histone deacetylases(HDAC) in skeletal muscle weakness in COPD. METHODS AND RESULTS: Twelve COPD patients, 8 smokers without COPD (SM) and 4 healthy non-smokers (NS) were recruited to the study. HDAC2 protein expression in quadriceps muscle biopsies of COPD patients (HDAC2/β-actin: 0...
May 19, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28525990/transversions-have-larger-regulatory-effects-than-transitions
#7
Cong Guo, Ian C McDowell, Michael Nodzenski, Denise M Scholtens, Andrew S Allen, William L Lowe, Timothy E Reddy
BACKGROUND: Transversions (Tv's) are more likely to alter the amino acid sequence of proteins than transitions (Ts's), and local deviations in the Ts:Tv ratio are indicative of evolutionary selection on genes. Whether the two different types of mutations have different effects in non-protein-coding sequences remains unknown. Genetic variants primarily impact gene expression by disrupting the binding of transcription factors (TFs) and other DNA-binding proteins. Because Tv's cause larger changes in the shape of a DNA backbone, we hypothesized that Tv's would have larger impacts on TF binding and gene expression...
May 19, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28525901/direct-inhibition-of-stat-signaling-by-platinum-drugs-contributes-to-their-anti-cancer-activity
#8
Stanleyson V Hato, Carl G Figdor, Susumu Takahashi, Anja E Pen, Altuna Halilovic, Kalijn F Bol, Angela Vasaturo, Yukie Inoue, Nienke de Haas, Dagmar Verweij, Carla M L Van Herpen, Johannes H Kaanders, Johan H J M van Krieken, Hanneke W M Van Laarhoven, Gerrit K J Hooijer, Cornelis J A Punt, Akira Asai, I Jolanda M de Vries, W Joost Lesterhuis
Platinum-based chemotherapeutics are amongst the most powerful anti-cancer drugs. Although their exact mechanism of action is not well understood, it is thought to be mediated through covalent DNA binding. We investigated the effect of platinum-based chemotherapeutics on signaling through signal transducer and activator of transcription (STAT) proteins, which are involved in many oncogenic signaling pathways. We performed in vitro experiments in various cancer cell lines, investigating the effects of platinum chemotherapeutics on STAT phosphorylation and nuclear translocation, the expression of STAT-modulating proteins and downstream signaling pathways...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525742/ubiquitin-modification-by-the-e3-ligase-adp-ribosyltransferase-dtx3l-parp9
#9
Chun-Song Yang, Kasey Jividen, Adam Spencer, Natalia Dworak, Li Ni, Luke T Oostdyk, Mandovi Chatterjee, Beata Kuśmider, Brian Reon, Mahmut Parlak, Vera Gorbunova, Tarek Abbas, Erin Jeffery, Nicholas E Sherman, Bryce M Paschal
ADP-ribosylation of proteins is emerging as an important regulatory mechanism. Depending on the family member, ADP-ribosyltransferases either conjugate a single ADP-ribose to a target or generate ADP-ribose chains. Here we characterize Parp9, a mono-ADP-ribosyltransferase reported to be enzymatically inactive. Parp9 undergoes heterodimerization with Dtx3L, a histone E3 ligase involved in DNA damage repair. We show that the Dtx3L/Parp9 heterodimer mediates NAD(+)-dependent mono-ADP-ribosylation of ubiquitin, exclusively in the context of ubiquitin processing by E1 and E2 enzymes...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28525739/genome-organization-cohesin-on-the-move
#10
Judita Richterova, Barbora Huraiova, Juraj Gregan
Folding of mammalian genomes into spatial domains is thought to depend on cohesin and CTCF proteins. Busslinger et al. (2017) reveal that transcription moves cohesin along DNA to CTCF-binding sites, providing insights into how cohesin and CTCF mediate chromosomal interactions by formation of chromatin loops.
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28525378/irf5-is-elevated-in-childhood-onset-sle-and-regulated-by-histone-acetyltransferase-and-histone-deacetylase-inhibitors
#11
Jin Shu, Ling Li, Lan-Bo Zhou, Jun Qian, Zhi-Dan Fan, Li-Li Zhuang, Lu-Lu Wang, Rui Jin, Hai-Guo Yu, Guo-Ping Zhou
Interferon regulatory factor 5 (IRF5) plays a critical role in the induction of type I interferon, proinflammatory cytokines and chemokines, and participates in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). However, the relationship between IRF5 and childhood-onset SLE remains elusive. In the present study, we demonstrated that levels of mRNA expression of IRF5, IFN-α, and Sp1 were significantly increased in childhood-onset SLE, as seen on quantitative real-time PCR, and the expression of Sp1 and IFN-α was positively correlated with IRF5...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524723/l1-retrotransposition-is-activated-by-ten-eleven-translocation-protein-1-and-repressed-by-methyl-cpg-binding-proteins
#12
Peng Zhang, Anne K Ludwig, Florian D Hastert, Cathia Rausch, Anne Lehmkuhl, Ines Hellmann, Martha Smets, Heinrich Leonhardt, M Cristina Cardoso
One of the major functions of DNA methylation is the repression of transposable elements, such as the long-interspersed nuclear element 1 (L1). The underlying mechanism(s), however, are unclear. Here, we addressed how retrotransposon activation and mobilization are regulated by methyl-cytosine modifying ten-eleven-translocation (Tet) proteins and how this is modulated by methyl-CpG binding domain (MBD) proteins. We show that Tet1 activates both, endogenous and engineered L1 retrotransposons. Furthermore, we found that Mecp2 and Mbd2 repress Tet1-mediated activation of L1 by preventing 5hmC formation at the L1 promoter...
May 19, 2017: Nucleus
https://www.readbyqxmd.com/read/28523558/epigenome-editing-in-the-brain
#13
Pavel Bashtrykov, Albert Jeltsch
Epigenome editing aims for an introduction or removal of chromatin marks at a defined genomic region using artificial EpiEffectors resulting in a modulation of the activity of the targeted functional DNA elements. Rationally designed EpiEffectors consist of a targeting DNA-binding module (such as a zinc finger protein, TAL effector, or CRISPR/Cas complex) and usually, but not exclusively, a catalytic domain of a chromatin-modifying enzyme. Epigenome editing opens a completely new strategy for basic research of the central nervous system and causal treatment of psychiatric and neurological diseases, because rewriting of epigenetic information can lead to the direct and durable control of the expression of disease-associated genes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523538/mecp2-a-modulator-of-neuronal-chromatin-organization-involved-in-rett-syndrome
#14
Alexia Martínez de Paz, Juan Ausió
From an epigenetic perspective, the genomic chromatin organization of neurons exhibits unique features when compared to somatic cells. Methyl CpG binding protein 2 (MeCP2), through its ability to bind to methylated DNA, seems to be a major player in regulating such unusual organization. An important contribution to this uniqueness stems from the intrinsically disordered nature of this highly abundant chromosomal protein in neurons. Upon its binding to methylated/hydroxymethylated DNA, MeCP2 is able to recruit a plethora of interacting protein and RNA partners...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523428/the-potential-role-of-kr%C3%A3-ppel-like-zinc-finger-protein-glis3-in-genetic-diseases-and-cancers
#15
REVIEW
Chon-Kit Chou, Chin-Ju Tang, Han-Lin Chou, Chun-Yen Liu, Ming-Chong Ng, Yu-Ting Chang, Shyng-Shiou F Yuan, Eing-Mei Tsai, Chien-Chih Chiu
Gli-similar 3 (Glis3) belongs to a Glis subfamily of Krüppel-like zinc-finger transcription factors characterized to regulate a set of downstream targets essential for cellular functions, including pancreatic development, β-cell maturation and maintenance, and insulin production. Examination of the DNA-binding domain of Glis3 reveals that this domain contains a repeated cysteine 2/histidine 2 (Cys2/His2) zinc-finger motif in the central region where the recognized DNA sequence binds. The loss of the production of pancreatic hormones, such as insulin 1 and 2, is linked to the down-regulation of β cells-related genes and promotes the apoptotic death of β cells found in mutant Glis3...
May 18, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28523272/structural-elements-regulating-aaa-protein-quality-control-machines
#16
REVIEW
Chiung-Wen Chang, Sukyeong Lee, Francis T F Tsai
Members of the ATPases Associated with various cellular Activities (AAA+) superfamily participate in essential and diverse cellular pathways in all kingdoms of life by harnessing the energy of ATP binding and hydrolysis to drive their biological functions. Although most AAA+ proteins share a ring-shaped architecture, AAA+ proteins have evolved distinct structural elements that are fine-tuned to their specific functions. A central question in the field is how ATP binding and hydrolysis are coupled to substrate translocation through the central channel of ring-forming AAA+ proteins...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28522586/antitumor-synergism-and-enhanced-survival-with-a-tumor-vasculature-targeted-enzyme-prodrug-system-rapamycin-and-cyclophosphamide
#17
John J Krais, Needa Virani, Partick H McKernan, Quang Nguyen, Kar-Ming Fung, Vassilios I Sikavitsas, Carla D Kurkjian, Roger G Harrison
Mutant cystathionine gamma-lyase was targeted to phosphatidylserine exposed on tumor vasculature through fusion with annexin A1 or annexin A5.  Cystathionine gamma-lyase E58N, R118L, and E338N mutations impart non-native methionine gamma-lyase activity, resulting in tumor-localized generation of highly toxic methylselenol upon systemic administration of non-toxic selenomethionine.  The described therapeutic system circumvents systemic toxicity issues using a novel drug delivery/generation approach and avoids the administration of non-native proteins and/or DNA required with other enzyme prodrug systems...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522430/the-drosophila-lin54-homolog-mip120-controls-two-aspects-of-oogenesis
#18
Mei-Hsin Cheng, Laura Andrejka, Paul J Vorster, Albert Hinman, Joseph S Lipsick
The conserved multi-protein MuvB core associates with the Myb oncoproteins and with the RB-E2F-DP tumor suppressor proteins in complexes that regulate cell proliferation, differentiation, and apoptosis. Drosophila Mip120, a homolog of LIN54, is a sequence-specific DNA-binding protein within the MuvB core. A mutant of Drosophila mip120 was previously shown to cause female and male sterility. We now show that Mip120 regulates two different aspects of oogenesis. First, in the absence of the Mip120 protein, egg chambers arrest during the transition from stage 7 to 8 with a failure of the normal program of chromosomal dynamics in the ovarian nurse cells...
May 18, 2017: Biology Open
https://www.readbyqxmd.com/read/28522396/ultrafast-spectroscopy-on-dna-cleavage-by-endonuclease-in-molecular-crowding
#19
Priya Singh, Susobhan Choudhury, Shreyasi Dutta, Aniruddha Adhikari, Siddhartha Bhattacharya, Debasish Pal, Samir Kumar Pal
The jam-packed intracellular environments differ the activity of a biological macromolecule from that in laboratory environments (in vitro) through a number of mechanisms called molecular crowding related to structure, function and dynamics of the macromolecule. Here, we have explored the structure, function and dynamics of a model enzyme protein DNase I in molecular crowing of polyethylene glycol (PEG; MW 3350). We have used steady state and picosecond resolved dynamics of a well-known intercalator ethidium bromide (EB) in a 20-mer double-stranded DNA (dsDNA) to monitor the DNA-cleavage by the enzyme in absence and presence PEG...
May 15, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28521084/design-of-modular-protein-tags-for-the-orthogonal-covalent-bond-formation-at-specific-dna-sequences
#20
Thang Minh Nguyen, Eiji Nakata, Masayuki Saimura, Huyen Dinh, Takashi Morii
Simultaneous formation of specific covalent linkages at nucleotides in given DNA sequences demand distinct orthogonal reactivity of DNA modification agents. Such highly specific reactions require well-balanced reactivity and affinity of the DNA modification agents. Conjugation of a sequence-specific DNA binding zinc finger protein and a self-ligating protein-tag provides a modular adaptor that expedites formation of a covalent bond between the protein-tag and a substrate-modified nucleotide at a specific DNA sequence...
May 18, 2017: Journal of the American Chemical Society
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