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Replication Stress

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https://www.readbyqxmd.com/read/28632741/aging-mortality-and-the-fast-growth-trade-off-of-schizosaccharomyces-pombe
#1
Hidenori Nakaoka, Yuichi Wakamoto
Replicative aging has been demonstrated in asymmetrically dividing unicellular organisms, seemingly caused by unequal damage partitioning. Although asymmetric segregation and inheritance of potential aging factors also occur in symmetrically dividing species, it nevertheless remains controversial whether this results in aging. Based on large-scale single-cell lineage data obtained by time-lapse microscopy with a microfluidic device, in this report, we demonstrate the absence of replicative aging in old-pole cell lineages of Schizosaccharomyces pombe cultured under constant favorable conditions...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28632080/lesbian-disclosure-and-health-care-seeking-in-the-united-states-a-replication-study
#2
Melissa St Pierre
The current study explored factors associated with lesbian disclosure to health care providers (HCPs) and engagement in preventative health behaviors by replicating and extending a Canadian path analysis study with a sample of U.S. lesbians. Both patient (education, feminism, global outness, and internalized homophobia) and HCP-related (lesbian-friendly HCPs and patient comfort) factors were either directly or indirectly associated with disclosure and engagement in preventative health behaviors, including avoidance of health-compromising behaviors (e...
February 17, 2017: Journal of Lesbian Studies
https://www.readbyqxmd.com/read/28631426/hsp90%C3%AE-regulates-atm-and-nbn-functions-in-sensing-and-repair-of-dna-double-strand-breaks
#3
Rosa Pennisi, Antonio Antoccia, Stefano Leone, Paolo Ascenzi, Alessandra di Masi
The molecular chaperone heat shock protein 90 (Hsp90α) regulates cells proteostasis and mitigates the harmful effects of endogenous and exogenous stressors on the proteome. Indeed, the inhibition of Hsp90α ATPase activity affects the cellular response to ionizing radiation (IR). Although the interplay between Hsp90α and several DNA damage response (DDR) proteins has been reported, its role in the DDR is still unclear. Here, we show that ATM and NBN, but not 53BP1, RAD50, and MRE11, are Hsp90α clients as the Hsp90α inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) induces ATM and NBN polyubiquitination and proteosomal degradation in normal fibroblasts and lymphoblastoid cells lines...
June 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28631015/ask-yeast-how-to-burn-your-fats-lessons-learned-from-the-metabolic-adaptation-to-salt-stress
#4
REVIEW
Amparo Pascual-Ahuir, Sara Manzanares-Estreder, Alba Timón-Gómez, Markus Proft
Here, we review and update the recent advances in the metabolic control during the adaptive response of budding yeast to hyperosmotic and salt stress, which is one of the best understood signaling events at the molecular level. This environmental stress can be easily applied and hence has been exploited in the past to generate an impressively detailed and comprehensive model of cellular adaptation. It is clear now that this stress modulates a great number of different physiological functions of the cell, which altogether contribute to cellular survival and adaptation...
June 19, 2017: Current Genetics
https://www.readbyqxmd.com/read/28630453/longitudinal-analyses-of-the-dna-methylome-in-deployed-military-servicemen-identify-susceptibility-loci-for-post-traumatic-stress-disorder
#5
B P F Rutten, E Vermetten, C H Vinkers, G Ursini, N P Daskalakis, E Pishva, L de Nijs, L C Houtepen, L Eijssen, A E Jaffe, G Kenis, W Viechtbauer, D van den Hove, K G Schraut, K-P Lesch, J E Kleinman, T M Hyde, D R Weinberger, L Schalkwyk, K Lunnon, J Mill, H Cohen, R Yehuda, D G Baker, A X Maihofer, C M Nievergelt, E Geuze, M P M Boks
In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions...
June 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28627616/distinct-cellular-phenotype-linked-to-defective-dna-interstrand-crosslink-repair-and-homologous-recombination
#6
Aleksandra M Gorniewska, Katarzyna Kluzek, Lidia Gackowska, Izabela Kubiszewska, Malgorzata Z Zdzienicka, Aneta Bialkowska
Repair of DNA interstrand crosslinks (ICLs) predominantly involves the Fanconi anemia (FA) pathway and homologous recombination (HR). The HR repair system eliminates DNA double strand breaks (DSBs) that emerge during ICLs removal. The current study presents a novel cell line, CL‑V8B, representing a new complementation group of Chinese hamster cell mutants hypersensitive to DNA crosslinking factors. CL‑V8B exhibits increased sensitivity to various DNA‑damaging agents, including compounds leading to DSBs formation (bleomycin and 6‑thioguanine), and is extremely sensitive to poly (ADP-ribose) polymerase inhibitor (>400‑fold), which is typical for HR‑defective cells...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627220/the-german-version-of-the-perceived-stress-scale-pss-10-evaluation-of-dimensionality-validity-and-measurement-invariance-with-exploratory-and-confirmatory-bifactor-modeling
#7
Dorota Reis, Dirk Lehr, Elena Heber, David Daniel Ebert
The Perceived Stress Scale (PSS) is a popular instrument for measuring the degree to which individuals appraise situations in their lives as excessively uncontrollable and overloaded. Despite its widespread use (e.g., for evaluating intervention effects in stress management studies), there is still no agreement on its factor structure. Hence, the aim of the present study was to examine the dimensionality, measurement invariance (i.e., across gender, samples, and time), reliability, and validity of the PSS. Data from 11,939 German adults (73% women) were used to establish an exploratory bifactor model for the PSS with one general and two specific factors and to cross-validate this model in a confirmatory bifactor model...
June 1, 2017: Assessment
https://www.readbyqxmd.com/read/28626638/transcriptome-of-barley-under-three-different-heavy-metal-stress-reaction
#8
Martina Kintlová, Nicolas Blavet, Radim Cegan, Roman Hobza
In the present study, we used Illumina sequencing technology (HiSeq 2000) to sequence the transcriptome of barley (Hordeum vulgare L., cv. Morex) under three different heavy metal stress conditions: copper, zinc and cadmium. For each of those metals, the concentration causing a 50% inhibitory effect for root growth (EC50) was determined. We sequenced the total RNA of both roots and shoots from barley with and without heavy metal treatments in three replicates. Raw reads of the transcriptome project have been deposited in NCBI's BioProject accession number PRJNA382490...
September 2017: Genomics Data
https://www.readbyqxmd.com/read/28626219/base-excision-repair-proteins-couple-activation-induced-cytidine-deaminase-and-endonuclease-g-during-replication-stress-induced-mll-destabilization
#9
B Gole, E Mian, M Rall, L Wiesmüller
The breakpoint cluster region of the MLL gene (MLLbcr) is frequently rearranged in therapy-related and infant acute leukaemia, but the destabilizing mechanism is poorly understood. We recently proposed that DNA replication stress results in MLLbcr cleavage via Endonuclease G (EndoG) and represents the common denominator of genotoxic therapy-induced MLL destabilization. Here we performed a siRNA screen for new factors involved in replication stress-induced MLL rearrangements employing an EGFP-based reporter system...
June 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28625494/acute-stress-shifts-the-balance-between-controlled-and-automatic-processes-in-prospective-memory
#10
Marcus Möschl, Moritz Walser, Franziska Plessow, Thomas Goschke, Rico Fischer
In everyday life we frequently rely on our abilities to postpone intentions until later occasions (prospective memory; PM) and to deactivate completed intentions even in stressful situations. Yet, little is known about the effects of acute stress on these abilities. In the present work we investigated the impact of acute stress on PM functioning under high task demands. 1) Different from previous studies, in which intention deactivation required mostly low processing demands, we used salient focal PM cues to induce high processing demands during intention-deactivation phases...
June 15, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28623975/mitochondrial-dna-content-and-methylation-in-fetal-cord-blood-of-pregnancies-with-placental-insufficiency
#11
Chiara Novielli, Chiara Mandò, Silvia Tabano, Gaia M Anelli, Laura Fontana, Patrizio Antonazzo, Monica Miozzo, Irene Cetin
INTRODUCTION: Intrauterine growth restriction (IUGR) and preeclampsia (PE) are pregnancy disorders characterized by placental insufficiency with oxygen/nutrient restriction and oxidative stress, all influencing mitochondria functionality and number. Moreover, IUGR and PE fetuses are predisposed to diseases later in life, and this might occur through epigenetic alterations. Here we analyze content and methylation of mitochondrial DNA (mtDNA), for the first time in IUGR and PE singleton fetuses, to identify possible alterations in mtDNA levels and/or epigenetic control of mitochondrial loci relevant to replication (D-loop) and functionality (mt-TF/RNR1: protein synthesis, mt-CO1: respiratory chain complex)...
July 2017: Placenta
https://www.readbyqxmd.com/read/28623093/the-role-of-smarcal1-in-replication-fork-stability-and-telomere-maintenance
#12
REVIEW
Natalia Lugli, Sotirios K Sotiriou, Thanos D Halazonetis
SMARCAL1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A-Like 1), also known as HARP, is an ATP-dependent annealing helicase that stabilizes replication forks during DNA damage. Mutations in this gene are the cause of Schimke immune-osseous dysplasia (SIOD), an autosomal recessive disorder characterized by T-cell immunodeficiency and growth dysfunctions. In this review, we summarize the main roles of SMARCAL1 in DNA repair, telomere maintenance and replication fork stability in response to DNA replication stress...
June 10, 2017: DNA Repair
https://www.readbyqxmd.com/read/28622519/replication-catastrophe-when-a-checkpoint-fails-because-of-exhaustion
#13
REVIEW
Luis Toledo, Kai John Neelsen, Jiri Lukas
Proliferating cells rely on the so-called DNA replication checkpoint to ensure orderly completion of genome duplication, and its malfunction may lead to catastrophic genome disruption, including unscheduled firing of replication origins, stalling and collapse of replication forks, massive DNA breakage, and, ultimately, cell death. Despite many years of intensive research into the molecular underpinnings of the eukaryotic replication checkpoint, the mechanisms underlying the dismal consequences of its failure remain enigmatic...
June 15, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28621305/structural-insights-into-the-function-of-zranb3-in-replication-stress-response
#14
Marek Sebesta, Christopher D O Cooper, Antonio Ariza, Christopher J Carnie, Dragana Ahel
Strategies to resolve replication blocks are critical for the maintenance of genome stability. Among the factors implicated in the replication stress response is the ATP-dependent endonuclease ZRANB3. Here, we present the structure of the ZRANB3 HNH (His-Asn-His) endonuclease domain and provide a detailed analysis of its activity. We further define PCNA as a key regulator of ZRANB3 function, which recruits ZRANB3 to stalled replication forks and stimulates its endonuclease activity. Finally, we present the co-crystal structures of PCNA with two specific motifs in ZRANB3: the PIP box and the APIM motif...
June 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28620461/the-enemies-within-regions-of-the-genome-that-are-inherently-difficult-to-replicate
#15
REVIEW
Rahul Bhowmick, Ian D Hickson
An unusual feature of many eukaryotic genomes is the presence of regions that appear intrinsically difficult to copy during the process of DNA replication. Curiously, the location of these difficult-to-replicate regions is often conserved between species, implying a valuable role in some aspect of genome organization or maintenance. The most prominent class of these regions in mammalian cells is defined as chromosome fragile sites, which acquired their name because of a propensity to form visible gaps/breaks on otherwise-condensed chromosomes in mitosis...
2017: F1000Research
https://www.readbyqxmd.com/read/28620052/the-antibacterial-prodrug-activator-rv2466c-is-a-mycothiol-dependent-reductase-in-the-oxidative-stress-response-of-mycobacterium-tuberculosis
#16
Leonardo Astolfi Rosado, Khadija Wahni, Giulia Degiacomi, Brandan Pedre, David Young, Alfonso G de la Rubia, Francesca Boldrin, Edo Martens, Laura Marcos-Pascual, Enea Sancho-Vaello, David Albesa-Jové, Roberta Provvedi, Charlotte Martin, Vadim Makarov, Wim Versées, Guido Verniest, Marcelo E Guerin, Luis M Mateos, Riccardo Manganelli, Joris Messens
The Mycobacterium tuberculosis rv2466c gene encodes an oxidoreductase enzyme annotated as DsbA. It has a CPWC active-site motif embedded within its thioredoxin-fold domain and mediates the activation of the prodrug TP053, a thienopyrimidine derivative that kills both replicating and nonreplicating bacilli. However, its mode of action and actual enzymatic function in M. tuberculosis have remained enigmatic. In this study, we report that Rv2466c is essential for bacterial survival under H2O2 stress. Further, we discovered that Rv2466c lacks oxidase activity; rather, it receives electrons through the mycothiol/mycothione reductase/NADPH pathway to activate TP053, preferentially via a dithiol-disulfide mechanism...
June 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28619751/synthesis-and-profiling-of-a-novel-potent-selective-inhibitor-of-chk1-kinase-possessing-unusual-n-trifluoromethylpyrazole-pharmacophore-resistant-to-metabolic-n-dealkylation
#17
Pounami Samadder, Tereza Suchanková, Ondrej Hylse, Prashant Khirsariya, Fedor Nikulenkov, Stanislav Drápela, Nicol Straková, Petr Vaňhara, Kateřina Vašíčková, Hana Kolářová, Lucia Binó, Miroslava Bittová, Petra Ovesná, Peter Kollar, Radek Fedr, Milan Ešner, Josef Jaroš, Aleš Hampl, Lumír Krejčí, Kamil Paruch, Karel Soucek
Checkpoint-mediated dependency of tumor cells can be deployed to selectively kill them without substantial toxicity to normal cells. Specifically, loss of CHK1, a serine threonine kinase involved in the surveillance of the G2/M checkpoint in the presence of replication stress inflicted by DNA damaging drugs, has been reported to dramatically influence the viability of tumor cells. CHK1's pivotal role in maintaining genomic stability offers attractive opportunity for increasing the selectivity, effectivity and reduced toxicity of chemotherapy...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28616176/adaptation-to-fluctuating-environments-in-a-selection-experiment-with-drosophila-melanogaster
#18
Olga I Kubrak, Sören Nylin, Thomas Flatt, Dick R Nässel, Olof Leimar
A fundamental question in life-history evolution is how organisms cope with fluctuating environments, including variation between stressful and benign conditions. For short-lived organisms, environments commonly vary between generations. Using a novel experimental design, we exposed wild-derived Drosophila melanogaster to three different selection regimes: one where generations alternated between starvation and benign conditions, and starvation was always preceded by early exposure to cold; another where starvation and benign conditions alternated in the same way, but cold shock sometimes preceded starvation and sometimes benign conditions; and a third where conditions were always benign...
June 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28615293/looping-out-mechanism-for-resolution-of-replicative-stress-at-telomeres
#19
Tianpeng Zhang, Zepeng Zhang, Feng Li, Qian Hu, Haiying Liu, Mengfan Tang, Wenbin Ma, Junjiu Huang, Zhou Songyang, Yikang Rong, Shichuan Zhang, Benjamin Pc Chen, Yong Zhao
Repetitive DNA is prone to replication fork stalling, which can lead to genome instability. Here, we find that replication fork stalling at telomeres leads to the formation of t-circle-tails, a new extrachromosomal structure that consists of circular telomeric DNA with a single-stranded tail. Structurally, the t-circle-tail resembles cyclized leading or lagging replication intermediates that are excised from the genome by topoisomerase II-mediated cleavage. We also show that the DNA damage repair machinery NHEJ is required for the formation of t-circle-tails and for the resolution of stalled replication forks, suggesting that NHEJ, which is normally constitutively suppressed at telomeres, is activated in the context of replication stress...
June 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28615194/fusion-fission-and-transport-control-asymmetric-inheritance-of-mitochondria-and-protein-aggregates
#20
Stefan Böckler, Xenia Chelius, Nadine Hock, Till Klecker, Madita Wolter, Matthias Weiss, Ralf J Braun, Benedikt Westermann
Partitioning of cell organelles and cytoplasmic components determines the fate of daughter cells upon asymmetric division. We studied the role of mitochondria in this process using budding yeast as a model. Anterograde mitochondrial transport is mediated by the myosin motor, Myo2. A genetic screen revealed an unexpected interaction of MYO2 and genes required for mitochondrial fusion. Genetic analyses, live-cell microscopy, and simulations in silico showed that fused mitochondria become critical for inheritance and transport across the bud neck in myo2 mutants...
June 14, 2017: Journal of Cell Biology
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