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DNA DAMAGE AND REPAIR

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https://www.readbyqxmd.com/read/28650656/cytotoxic-and-mutagenic-properties-of-c3-epimeric-lesions-of-2-deoxyribonucleosides-in-escherichia-coli-cells
#1
Pengcheng Wang, Nicholas J Amato, Yinsheng Wang
Reactive oxygen species (ROS), resulting from endogenous metabolism and/or environmental exposure, can induce damage to the 2-deoxyribose moiety in DNA. Specifically, a hydrogen atom from each of the five carbon atoms in 2-deoxyribose can be abstracted by hydroxyl radical, and improper chemical repair of the ensuing radicals formed at the C1', C3', and C4' positions can lead to the stereochemical inversion at these carbons to yield epimeric 2-deoxyribose lesions. Although single-nucleobase lesions induced by ROS have been well characterized, few studies have been conducted to examine the biological consequences of the C3'-epimeric lesions of 2'-deoxynucleosides, i...
June 26, 2017: Biochemistry
https://www.readbyqxmd.com/read/28650317/serine-adp-ribosylation-reversal-by-the-hydrolase-arh3
#2
Ivan Ahel, Pietro Fontana, Juan José Bonfiglio, Luca Palazzo, Edward Bartlett, Ivan Matic
ADP-ribosylation (ADPr) is a posttranslational modification (PTM) of proteins that controls many cellular processes, including DNA repair, transcription, chromatin regulation and mitosis. A number of proteins catalyse the transfer and hydrolysis of ADPr, and also specify how and when the modification is conjugated to the targets. We recently discovered a new form of ADPr that is attached to serine residues in target proteins (Ser-ADPr) and showed that this PTM is specifically made by PARP1/HPF1 and PARP2/HPF1 complexes...
June 26, 2017: ELife
https://www.readbyqxmd.com/read/28650265/autophagy-regulates-dna-repair-through-sqstm1-p62
#3
Yuchen Feng, Daniel J Klionsky
Macroautophagy/autophagy is primarily a degradative pathway that clears malfunctioning cellular components in response to various types of stress. Recent studies have indicated that autophagy also plays an important role in maintaining genome stability. Loss of autophagy is associated with increased damage to DNA, inappropriate amplification of genomic regions and abnormal chromosome number. In a recent paper by Wang et al. the authors uncover a mechanism through which autophagy regulates the ubiquitination of chromatin...
June 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28649742/genotranscriptomic-meta-analysis-of-the-chd-family-chromatin-remodelers-in-human-cancers-initial-evidence-of-an-oncogenic-role-for-chd7
#4
Xiaofang Chu, Xuhui Guo, Yuanyuan Jiang, Huimei Yu, Lanxin Liu, Wenqi Shan, Zeng-Quan Yang
Chromodomain helicase DNA binding proteins (CHD) are characterized by N-terminal tandem chromodomains and a central ATP-dependent helicase domain. CHDs govern the cellular machinery's access to DNA, thereby playing critical roles in various cellular processes including transcription, proliferation, and DNA damage repair. Accumulating evidence demonstrates that mutation and dysregulation of CHDs are implicated in the pathogenesis of developmental disorders and cancer. However, we know little about genomic and transcriptomic alterations and the clinical significance of most CHDs in human cancer...
June 26, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28649636/interplay-of-space-radiation-and-microgravity-in-dna-damage-and-dna-damage-response
#5
María Moreno-Villanueva, Michael Wong, Tao Lu, Ye Zhang, Honglu Wu
In space, multiple unique environmental factors, particularly microgravity and space radiation, pose constant threat to the DNA integrity of living organisms. Specifically, space radiation can cause damage to DNA directly, through the interaction of charged particles with the DNA molecules themselves, or indirectly through the production of free radicals. Although organisms have evolved strategies on Earth to confront such damage, space environmental conditions, especially microgravity, can impact DNA repair resulting in accumulation of severe DNA lesions...
2017: NPJ Microgravity
https://www.readbyqxmd.com/read/28649423/ubiquitous-overexpression-of-the-dna-repair-factor-dprp19-reduces-dna-damage-and-extends-drosophila-life-span
#6
Kathrin Garschall, Hanna Dellago, Martina Gáliková, Markus Schosserer, Thomas Flatt, Johannes Grillari
Mechanisms that ensure and maintain the stability of genetic information are fundamentally important for organismal function and can have a large impact on disease, aging, and life span. While a multi-layered cellular apparatus exists to detect and respond to DNA damage, various insults from environmental and endogenous sources continuously affect DNA integrity. Over time this can lead to the accumulation of somatic mutations, which is thought to be one of the major causes of aging. We have previously found that overexpression of the essential human DNA repair and splicing factor SNEV, also called PRP19 or hPso4, extends replicative life span of cultured human endothelial cells and impedes accumulation of DNA damage...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28649007/polypharmacy-and-sun-exposure-implications-for-mitochondrial-dna-deletions-in-skin
#7
Julia Montelin Powers, Gillian Murphy, Nikki Ralph, Susan M O'Gorman, James E J Murphy
Most somatic cells contain many copies of mitochondrial DNA (mtDNA). Because of both the high copy number and the lack of repair mechanisms available to mtDNA, damage to it largely goes unrepaired, and can accumulate over time. Large scale deletions are a recognised type of damage sustained by mtDNA as a consequence of exposure to the ultraviolet light in sunlight. A group of patients were identified as having abnormally high levels of either a 4977 base pair deletion (mtDNA(4977)) or 3895 base pair deletion (mtDNA(3895)), in mtDNA from sun exposed skin or skin suspected to be a non-melanoma skin cancer, but not in their non-sun exposed skin biopsies...
June 17, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28647894/keratin-gene-mutations-influence-the-keratinocyte-response-to-dna-damage-and-cytokine-induced-apoptosis
#8
Tina Zupancic, Gregor Sersa, Hans Törmä, Ellen Birgitte Lane, Harald Herrmann, Radovan Komel, Mirjana Liovic
The keratin filament cytoskeleton is vital to the normal function of epithelial cells. It provides structural support and regulates different aspects of cell metabolism. Mutations in keratins 5 and 14 cause a skin fragility disorder, epidermolysis bullosa simplex (EBS). Patients with severe EBS have an increased cumulative risk for basal cell carcinoma. In this study, we tested how keratin 5 and 14 mutant EBS patient-derived keratinocytes behave in the face of two different types of stressors that are able to induce cell death: ionizing radiation and cytokines TNF-α and TRAIL...
June 24, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28646736/cell-damage-caused-by-ultraviolet-b-radiation-in-the-desert-cyanobacterium-phormidium-tenue-and-its-recovery-process
#9
Gaohong Wang, Songqiang Deng, Jiafeng Liu, Chaoran Ye, Xiangjun Zhou, Lanzhou Chen
Phormidium tenue, a cyanobacterium that grows in the topsoil of biological soil crusts (BSCs), has the highest recovery rate among desert crust cyanobacteria after exposure to ultraviolet B (UV-B) radiation. However, the mechanism underlying its recovery process is unclear. To address this issue, we measured chlorophyll a fluorescence, generation of reactive oxygen species (ROS), lipid peroxidation, and repair of DNA breakage in P. tenue following exposure to UV-B. We found that UV-B radiation at all doses tested reduced photosynthesis and induced cell damage in P...
June 21, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28646223/regular-exercise-participation-improves-genomic-stability-in-diabetic-patients-an-exploratory-study-to-analyse-telomere-length-and-dna-damage
#10
Ivan Dimauro, Antonella Sgura, Monica Pittaluga, Fiorenza Magi, Cristina Fantini, Rosa Mancinelli, Antonio Sgadari, Stefania Fulle, Daniela Caporossi
Physical activity has been demonstrated to be effective in the prevention and treatment of different chronic conditions, including type 2 diabetes (T2D). In particular, several studies highlighted how the beneficial effects of physical activity may be related to the stability of the DNA molecule, such as longer telomeric ends. Here we analyze the effect of exercise training on telomere length, spontaneous and H2O2-induced DNA damage, as well as the apoptosis level in leukocytes from untrained or trained T2D patients vs...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646114/staphylococcus-aureus-strain-newman-photoinactivation-and-cellular-response-to-sunlight-exposure
#11
Jill S McClary, Lauren M Sassoubre, Alexandria B Boehm
Sunlight influences microbial water quality of surface waters. Previous studies have investigated photoinactivation mechanisms and cellular photostress responses of fecal indicator bacteria (FIB), including Escherichia coli and enterococci, but further work is needed to characterize photostress responses of bacterial pathogens. Here we investigate the photoinactivation of Staphylococcus aureus (strain Newman), a pigmented, waterborne pathogen of emerging concern. We measured photodecay using standard culture-based assays and cellular membrane integrity; and investigated photostress response by measuring the relative number of mRNA transcripts of select oxidative stress, DNA repair, and metabolism genes...
June 23, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28646091/stress-specific-p38-map-kinase-activation-is-sufficient-to-drive-egf-receptor-endocytosis-but-not-nuclear-translocation
#12
Alejandra Tomas, Sylwia Jones, Simon O Vaughan, Daniel Hochhauser, Clare E Futter
P38 MAP kinase-dependent EGF receptor (EGFR) endocytosis is induced by stress. Ligand and stresses like X-rays, reportedly promote nuclear traffic of endocytosed EGFR for regulation of gene transcription and DNA repair. We fail to detect EGFR endocytosis or nuclear transport following X-ray treatment of HeLa or head and neck cancer cells, despite extensive DNA damage induction. Apparent nuclear staining with EGFR extracellular domain antibody remained present despite reduced/absent EGFR expression and so did not represent nuclear EGFR...
June 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28645380/comet-fish-for-ultrasensitive-strand-specific-detection-of-dna-damage-in-single-cells
#13
Manas Mondal, Jia Guo
The genome integrity of living organisms is constantly threatened by endogenous cellular metabolic processes and environmental agents. To quantify these low, physiologically relevant levels of DNA damage, a single-cell gel electrophoresis (comet) combined with strand-specific fluorescence in situ hybridization (FISH)-based approach has been developed. This approach enables the quantification of low levels of specific DNA lesions in each strand of the selected sequence at the single-molecule sensitivity, as well as in the genome overall in single cells...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28645375/current-and-emerging-assays-for-studying-the-primer-synthesis-activities-of-dna-primases
#14
Thomas A Guilliam, Aidan J Doherty
Primases play a crucial role in the initiation of DNA synthesis during replication by de novo synthesis of short RNA or DNA "primers." In recent years, evidence has accumulated which expands the essential roles of primases to include, not only the initiation of replication but also other critical roles in DNA metabolism, including damage tolerance and repair. Despite the broadening roles for these enzymes, the methods used to identify and characterize primase activities are limited. Historically, biochemical analysis of primases has been based on the synthesis of radioactively labeled primers and their detection on denaturing polyacrylamide gels...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28645370/xenopus-laevis-as-model-system-to-study-dna-damage-response-and-replication-fork-stability
#15
Vincenzo Sannino, Federica Pezzimenti, Stefania Bertora, Vincenzo Costanzo
Although many players of the DNA damage response and DNA repair have been identified in several systems their biochemical role is still poorly understood. The use of the Xenopus laevis egg extract cell-free system allowed biochemical dissection of DNA replication and cell cycle events in a complex biological context. The possibility of manipulating the protein content by using protein depletion procedures makes egg extract a powerful system to study proteins whose inactivation results in cellular lethality...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28645367/base-excision-repair-variants-in-cancer
#16
Carolyn G Marsden, Julie A Dragon, Susan S Wallace, Joann B Sweasy
Base excision repair (BER) is a key genome maintenance pathway that removes endogenously damaged DNA bases that arise in cells at very high levels on a daily basis. Failure to remove these damaged DNA bases leads to increased levels of mutagenesis and chromosomal instability, which have the potential to drive carcinogenesis. Next-generation sequencing of the germline and tumor genomes of thousands of individuals has uncovered many rare mutations in BER genes. Given that BER is critical for genome maintenance, it is important to determine whether BER genomic variants have functional phenotypes...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28645083/graphene-oxide-nanosheets-induce-dna-damage-and-activate-the-base-excision-repair-ber-signaling-pathway-both-in%C3%A2-vitro-and-in%C3%A2-vivo
#17
Chun-Jiao Lu, Xue-Feng Jiang, Muhammad Junaid, Yan-Bo Ma, Pan-Pan Jia, Hua-Bin Wang, De-Sheng Pei
Graphene oxide (GO) has widespread concerns in the fields of biological sciences and medical applications. Currently, studies have reported that excessive GO exposure can cause cellular DNA damage through reactive oxygen species (ROS) generation. However, DNA damage mediated response of the base excision repair (BER) pathway due to GO exposure is not elucidated yet. Therefore, we exposed HEK293T cells and zebrafish embryos to different concentrations of GO for 24 h, and transcriptional profiles of BER pathway genes, DNA damage, and cell viability were analyzed both in vitro and in vivo...
June 14, 2017: Chemosphere
https://www.readbyqxmd.com/read/28644902/sirt6-alters-adult-hippocampal-neurogenesis
#18
Eitan Okun, Daniel Marton, Daniel Cohen, Kathleen Griffioen, Yariv Kanfi, Tomer Illouz, Ravit Madar, Haim Y Cohen
Sirtuins are pleiotropic NAD+ dependent histone deacetylases involved in metabolism, DNA damage repair, inflammation and stress resistance. SIRT6, a member of the sirtuin family, regulates the process of normal aging and increases the lifespan of male mice over-expressing Sirt6 by 15%. Neurogenesis, the formation of new neurons within the hippocampus of adult mammals, involves several complex stages including stem cell proliferation, differentiation, migration and network integration. During aging, the number of newly generated neurons continuously declines, and this is correlated with a decline in neuronal plasticity and cognitive behavior...
2017: PloS One
https://www.readbyqxmd.com/read/28644590/mutyh-associated-polyposis-the-irish-experience
#19
T P McVeigh, M Duff, C Carroll, R O'Shea, L Bradley, M Farrell, D J Gallagher, C Clabby, A J Green
MUTYH is involved in DNA damage repair. Bi-allelic MUTYH mutations predispose to polyposis and gastrointestinal malignancies, distinct genetically from autosomal dominant familial adenomatous polyposis coli. Two common European MUTYH mutations account for 90% of MUTYH-associated polyposis (MAP). We aimed to examine the incidence of MAP in Ireland. A retrospective cohort study was undertaken. Patients undergoing MUTYH testing from 2003-2016 were identified by searching electronic databases using terms "MUTYH" and "MYH"...
December 12, 2016: Irish Medical Journal
https://www.readbyqxmd.com/read/28644387/rna-binding-proteins-and-genome-integrity
#20
REVIEW
Kensei Nishida, Yuki Kuwano, Tatsuya Nishikawa, Kiyoshi Masuda, Kazuhito Rokutan
Genome integrity can be threatened by various endogenous or exogenous events. To counteract these stressors, the DNA damage response network contributes to the prevention and/or repair of genomic DNA damage and serves an essential function in cellular survival. DNA binding proteins are involved in this network. Recently, several RNA-binding proteins (RBPs) that are recruited to DNA damage sites have been shown to be direct players in the prevention or repair of DNA damage. In addition, non-coding RNAs, themselves, are involved in the RNA-mediated DNA repair system...
June 23, 2017: International Journal of Molecular Sciences
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