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https://www.readbyqxmd.com/read/28230817/common%C3%A2-chemical%C3%A2-inductors%C3%A2-of%C3%A2-replication%C3%A2-stress-%C3%A2-focus%C3%A2-on%C3%A2-cell-based%C3%A2-studies
#1
REVIEW
Eva Vesela, Katarina Chroma, Zsofia Turi, Martin Mistrik
DNA replication is a highly demanding process regarding the energy and material supply and must be precisely regulated, involving multiple cellular feedbacks. The slowing down or stalling of DNA synthesis and/or replication forks is referred to as replication stress (RS). Owing to the complexity and requirements of replication, a plethora of factors may interfere and challenge the genome stability, cell survival or affect the whole organism. This review outlines chemical compounds that are known inducers of RS and commonly used in laboratory research...
February 21, 2017: Biomolecules
https://www.readbyqxmd.com/read/28230815/conceptual-foundations-of-systems-biology-explaining-complex-cardiac-diseases
#2
REVIEW
George E Louridas, Katerina G Lourida
Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine...
February 21, 2017: Healthcare (Basel, Switzerland)
https://www.readbyqxmd.com/read/28230529/single-molecule-fret-unveils-induced-fit-mechanism-for-substrate-selectivity-in-flap-endonuclease-1
#3
Fahad Rashid, Paul D Harris, Manal S Zaher, Mohamed A Sobhy, Luay I Joudeh, Chunli Yan, Hubert Piwonski, Susan E Tsutakawa, Ivaylo Ivanov, John A Tainer, Satoshi Habuchi, Samir M Hamdan
Human flap endonuclease 1 (FEN1) and related structure-specific 5'nucleases precisely identify and incise aberrant DNA structures during replication, repair and recombination to avoid genomic instability. Yet, it is unclear how the 5'nuclease mechanisms of DNA distortion and protein ordering robustly mediate efficient and accurate substrate recognition and catalytic selectivity. Here, single-molecule sub-millisecond and millisecond analyses of FEN1 reveal a protein-DNA induced-fit mechanism that efficiently verifies substrate and suppresses off-target cleavage...
February 23, 2017: ELife
https://www.readbyqxmd.com/read/28229978/untranslated-regions-of-mrna-and-their-role-in-regulation-of-gene-expression-in-protozoan-parasites
#4
Shilpa J Rao, Sangeeta Chatterjee, Jayantapal K Pal
Protozoan parasites are one of the oldest living entities in this world that throughout their existence have shown excellent resilience to the odds of survival and have adapted beautifully to ever changing rigors of the environment. In view of the dynamic environment encountered by them throughout their life cycle, and in establishing pathogenesis, it is unsurprising that modulation of gene expression plays a fundamental role in their survival. In higher eukaryotes, untranslated regions (UTRs) of transcripts are one of the crucial regulators of gene expression (influencing mRNA stability and translation efficiency)...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28229048/anaplasma-phagocytophilum-infection-subverts-carbohydrate-metabolic-pathways-in-the-tick-vector-ixodes-scapularis
#5
Alejandro Cabezas-Cruz, Pilar Alberdi, James J Valdés, Margarita Villar, José de la Fuente
The obligate intracellular pathogen, Anaplasma phagocytophilum, is the causative agent of human, equine, and canine granulocytic anaplasmosis and tick-borne fever (TBF) in ruminants. A. phagocytophilum has become an emerging tick-borne pathogen in the United States, Europe, Africa, and Asia, with increasing numbers of infected people and animals every year. It has been recognized that intracellular pathogens manipulate host cell metabolic pathways to increase infection and transmission in both vertebrate and invertebrate hosts...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28228589/capsid-phosphorylation-state-and-hepadnavirus-virion-secretion
#6
Xiaojun Ning, Suresh H Basagoudanavar, Kuancheng Liu, Laurie Luckenbaugh, Duoqian Wei, Chunyan Wang, Bo Wei, Yingren Zhao, Taotao Yan, William Delaney, Jianming Hu
The C-terminal domain (CTD) of hepadnavirus core protein is involved in multiple steps of viral replication. In particular, CTD is initially phosphorylated at multiple sites to facilitate viral RNA packaging into immature nucleocapsids (NCs) and the early stage of viral DNA synthesis. For the avian hepadnavirus, the duck hepatitis B virus (DHBV), CTD is dephosphorylated subsequently to facilitate the late stage of viral DNA synthesis and to stabilize NCs containing mature viral DNA. The role of CTD phosphorylation in virion secretion, if any, has remained unclear...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28228534/topbp1-dpb11-plays-a-conserved-role-in-homologous-recombination-dna-repair-through-the-coordinated-recruitment-of-53bp1-rad9
#7
Yi Liu, José Renato Cussiol, Diego Dibitetto, Jennie Rae Sims, Shyam Twayana, Robert Samuel Weiss, Raimundo Freire, Federica Marini, Achille Pellicioli, Marcus Bustamante Smolka
Genome maintenance and cancer suppression require homologous recombination (HR) DNA repair. In yeast and mammals, the scaffold protein TOPBP1(Dpb11) has been implicated in HR, although its precise function and mechanism of action remain elusive. In this study, we show that yeast Dpb11 plays an antagonistic role in recombination control through regulated protein interactions. Dpb11 mediates opposing roles in DNA end resection by coordinating both the stabilization and exclusion of Rad9 from DNA lesions. The Mec1 kinase promotes the pro-resection function of Dpb11 by mediating its interaction with the Slx4 scaffold...
February 22, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28228480/a-stable-but-reversible-integrated-surrogate-reporter-for-assaying-crispr-cas9-stimulated-homology-directed-repair
#8
Yahong Wen, Grace Liao, Thomas Pritchard, Ting-Ting Zhao, Jon P Connelly, Shondra M Pruett-Miller, Valerie Blanc, Nicholas O Davidson, Blair B Madison
The discovery and application of CRISPR/Cas9 technology for genome editing has greatly accelerated targeted mutagenesis in a variety of organisms. CRISPR/Cas9-mediated site-specific cleavage is typically exploited for the generation of insertions or deletions (indels) following aberrant dsDNA repair via the endogenous non-homology end-joining (NHEJ) pathway, or alternatively, for enhancing homology directed repair (HDR) to facilitate the generation of a specific mutation (or knock-in). However, there is a need for efficient cellular assays that can measure Cas9/guide RNA (gRNA) activity...
February 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28228263/reciprocal-regulation-between-53bp1-and-the-anaphase-promoting-complex-cyclosome-is-required-for-genomic-stability-during-mitotic-stress
#9
Thomas J Kucharski, Paul E Minshall, Mohamed Moustafa-Kamal, Andrew S Turnell, Jose G Teodoro
The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that targets substrates for degradation to promote mitotic progression. Here, we show that the DNA damage response protein 53BP1 contains conserved KEN boxes that are required for APC/C-dependent degradation in early mitosis. Mutation of the 53BP1 KEN boxes stabilized the protein and extended mitotic duration, whereas 53BP1 knockdown resulted in a shorter and delayed mitosis. Loss of 53BP1 increased APC/C activity, and we show that 53BP1 is a direct APC/C inhibitor...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28226235/plant-mitochondrial-genomes-dynamics-and-mechanisms-of-mutation
#10
José M Gualberto, Kathleen J Newton
The large mitochondrial genomes of angiosperms are unusually dynamic because of recombination activities involving repeated sequences. These activities generate subgenomic forms and extensive genomic variation even within the same species. Such changes in genome structure are responsible for the rapid evolution of plant mitochondrial DNA and for the variants associated with cytoplasmic male sterility and abnormal growth phenotypes. Nuclear genes modulate these processes, and over the past decade, several of these genes have been identified...
February 9, 2017: Annual Review of Plant Biology
https://www.readbyqxmd.com/read/28225080/dna-g-quadruplexes-in-the-human-genome-detection-functions-and-therapeutic-potential
#11
REVIEW
Robert Hänsel-Hertsch, Marco Di Antonio, Shankar Balasubramanian
Single-stranded guanine-rich DNA sequences can fold into four-stranded DNA structures called G-quadruplexes (G4s) that arise from the self-stacking of two or more guanine quartets. There has been considerable recent progress in the detection and mapping of G4 structures in the human genome and in biologically relevant contexts. These advancements, many of which align with predictions made previously in computational studies, provide important new insights into the functions of G4 structures in, for example, the regulation of transcription and genome stability, and uncover their potential relevance for cancer therapy...
February 22, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28223401/transcriptome-analyses-of-rhesus-monkey-pre-implantation-embryos-reveal-a-reduced-capacity-for-dna-double-strand-break-repair-in-primate-oocytes-and-early-embryos
#12
Xinyi Wang, Denghui Liu, Dajian He, Shengbo Suo, Xian Xia, Xiechao He, Jing-Dong Han, Ping Zheng
Pre-implantation embryogenesis encompasses several critical events including genome reprogramming, zygotic genome activation (ZGA), and cell fate commitment, most of which remain mechanistically unclear in primates. In addition, primates display a high rate of embryo wastage without any clear molecular basis. Understanding the factors involved in genome reprogramming and ZGA will help the generation of induced pluripotent stem cells with high efficiency. Moreover, explaining the molecular basis responsible for embryo wastage in primates will greatly expand our knowledge of species evolution...
February 21, 2017: Genome Research
https://www.readbyqxmd.com/read/28223399/centromere-location-in-arabidopsis-is-unaltered-by-extreme-divergence-in-cenh3-protein-sequence
#13
Shamoni Maheshwari, Takayoshi Ishii, C Titus Brown, Andreas Houben, Luca Comai
During cell division, spindle fibers attach to chromosomes at centromeres. The DNA sequence at regional centromeres is fast evolving with no conserved genetic signature for centromere identity. Instead CENH3, a centromere-specific histone H3 variant, is the epigenetic signature that specifies centromere location across both plant and animal kingdoms. Paradoxically, CENH3 is also adaptively evolving. An ongoing question is whether CENH3 evolution is driven by a functional relationship with the underlying DNA sequence...
February 21, 2017: Genome Research
https://www.readbyqxmd.com/read/28220209/s-phase-checkpoint-regulations-that-preserve-replication-and-chromosome-integrity-upon-dntp-depletion
#14
REVIEW
Michele Giannattasio, Dana Branzei
DNA replication stress, an important source of genomic instability, arises upon different types of DNA replication perturbations, including those that stall replication fork progression. Inhibitors of the cellular pool of deoxynucleotide triphosphates (dNTPs) slow down DNA synthesis throughout the genome. Following depletion of dNTPs, the highly conserved replication checkpoint kinase pathway, also known as the S-phase checkpoint, preserves the functionality and structure of stalled DNA replication forks and prevents chromosome fragmentation...
February 20, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28220109/temporal-stability-and-the-effect-of-transgenerational-transfer-on-fecal-microbiota-structure-in-a-long-distance-migratory-bird
#15
Jakub Kreisinger, Lucie Kropáčková, Adéla Petrželková, Marie Adámková, Oldřich Tomášek, Jean-François Martin, Romana Michálková, Tomáš Albrecht
Animal bodies are inhabited by a taxonomically and functionally diverse community of symbiotic and commensal microorganisms. From an ecological and evolutionary perspective, inter-individual variation in host-associated microbiota contributes to physiological and immune system variation. As such, host-associated microbiota may be considered an integral part of the host's phenotype, serving as a substrate for natural selection. This assumes that host-associated microbiota exhibits high temporal stability, however, and that its composition is shaped by trans-generational transfer or heritable host-associated microbiota modulators encoded by the host genome...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28219007/electrochemistry-of-the-4fe4s-cluster-in-base-excision-repair-proteins-tuning-the-redox-potential-with-dna
#16
Phillip Leon Bartels, Andy Zhou, Anna Ruth Arnold, Nicole N Nunez, Frank Nelson Crespilho, Sheila S David, Jacqueline K Barton
Escherichia coli Endonuclease III (EndoIII) and MutY are DNA glycosylases that contain [4Fe4S] clusters and that serve to maintain the integrity of the genome after oxidative stress. Electrochemical studies on highly-oriented pyrolytic graphite (HOPG) revealed that DNA binding by EndoIII leads to a large negative shift in midpoint potential of the cluster, consistent with stabilization of the oxidized [4Fe4S]3+ form. However, the smooth, hydrophobic HOPG surface is non-ideal for working with proteins in the absence of DNA...
February 20, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28218992/differently-localized-lysophosphatidic-acid-acyltransferases-crucial-for-triacylglycerol-biosynthesis-in-the-oleaginous-alga-nannochloropsis
#17
Takashi Nobusawa, Koichi Hori, Hiroshi Mori, Ken Kurokawa, Hiroyuki Ohta
Production of renewable bioenergy will be necessary to meet rising global fossil fuel demands. Members of the marine microalgae genus Nannochloropsis produce large amounts of oils (triacylglycerols; TAGs), and this genus is regarded as one of the most promising for biodiesel production. Recent genome sequencing and transcriptomic studies on Nannochloropsis have provided a foundation for understanding its oleaginous trait, but the mechanism underlying oil accumulation remains to be clarified. Here we report Nannochloropsis knockout strains of four extraplastidic lysophosphatidic acid acyltransferases (LPAT1-4), which catalyze a major de novo biosynthetic step of TAGs and membrane lipids...
February 20, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28218681/the-intra-s-checkpoint-responses-to-dna-damage
#18
REVIEW
Divya Ramalingam Iyer, Nicholas Rhind
Faithful duplication of the genome is a challenge because DNA is susceptible to damage by a number of intrinsic and extrinsic genotoxins, such as free radicals and UV light. Cells activate the intra-S checkpoint in response to damage during S phase to protect genomic integrity and ensure replication fidelity. The checkpoint prevents genomic instability mainly by regulating origin firing, fork progression, and transcription of G1/S genes in response to DNA damage. Several studies hint that regulation of forks is perhaps the most critical function of the intra-S checkpoint...
February 17, 2017: Genes
https://www.readbyqxmd.com/read/28218679/mcm10-a-dynamic-scaffold-at-eukaryotic-replication-forks
#19
REVIEW
Ryan M Baxley, Anja-Katrin Bielinsky
To complete the duplication of large genomes efficiently, mechanisms have evolved that coordinate DNA unwinding with DNA synthesis and provide quality control measures prior to cell division. Minichromosome maintenance protein 10 (Mcm10) is a conserved component of the eukaryotic replisome that contributes to this process in multiple ways. Mcm10 promotes the initiation of DNA replication through direct interactions with the cell division cycle 45 (Cdc45)-minichromosome maintenance complex proteins 2-7 (Mcm2-7)-go-ichi-ni-san GINS complex proteins, as well as single- and double-stranded DNA...
February 17, 2017: Genes
https://www.readbyqxmd.com/read/28216432/epigenetic-modification-by-dietary-factors-implications-in-metabolic-syndrome
#20
REVIEW
Jae-Ho Park, Soon-Hee Kim, Myeong Soo Lee, Myung-Sunny Kim
Dietary factors play a role in normal biological processes and are involved in the regulation of pathological progression over a lifetime. Evidence has emerged indicating that dietary factor-dependent epigenetic modifications can significantly affect genome stability and the expression of mRNA and proteins, which are involved in metabolic dysfunction. Since metabolic syndrome is a progressive phenotype characterized by insulin resistance, obesity, hypertension, dyslipidemia, or type 2 diabetes, gene-diet interactions are important processes involved in the initiation of particular symptoms of metabolic syndrome and their progression...
February 16, 2017: Molecular Aspects of Medicine
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