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https://www.readbyqxmd.com/read/28535251/mms1-binds-to-g-rich-regions-in-saccharomyces-cerevisiae-and-influences-replication-and-genome-stability
#1
Katharina Wanzek, Eike Schwindt, John A Capra, Katrin Paeschke
The regulation of replication is essential to preserve genome integrity. Mms1 is part of the E3 ubiquitin ligase complex that is linked to replication fork progression. By identifying Mms1 binding sites genome-wide in Saccharomyces cerevisiae we connected Mms1 function to genome integrity and replication fork progression at particular G-rich motifs. This motif can form G-quadruplex (G4) structures in vitro. G4 are stable DNA structures that are known to impede replication fork progression. In the absence of Mms1, genome stability is at risk at these G-rich/G4 regions as demonstrated by gross chromosomal rearrangement assays...
May 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28535155/elevated-apobec3b-expression-drives-a-kataegic-like-mutation-signature-and-replication-stress-related-therapeutic-vulnerabilities-in-p53-defective-cells
#2
Jenni Nikkilä, Rahul Kumar, James Campbell, Inger Brandsma, Helen N Pemberton, Fredrik Wallberg, Kinga Nagy, Ildikó Scheer, Beata G Vertessy, Artur A Serebrenik, Valentina Monni, Reuben S Harris, Stephen J Pettitt, Alan Ashworth, Christopher J Lord
BACKGROUND: Elevated APOBEC3B expression in tumours correlates with a kataegic pattern of localised hypermutation. We assessed the cellular phenotypes associated with high-level APOBEC3B expression and the influence of p53 status on these phenotypes using an isogenic system. METHODS: We used RNA interference of p53 in cells with inducible APOBEC3B and assessed DNA damage response (DDR) biomarkers. The mutational effects of APOBEC3B were assessed using whole-genome sequencing...
May 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28535027/arsenite-binds-to-the-ring-finger-domain-of-fancl-e3-ubiquitin-ligase-and-inhibits-dna-interstrand-cross-link-repair
#3
Ji Jiang, Marina Bellani, Lin Li, Pengcheng Wang, Michael M Seidman, Yinsheng Wang
Human exposure to arsenic in drinking water is known to be associated with the development of bladder, lung, kidney, and skin cancers. The molecular mechanisms underlying the carcinogenic effects of arsenic species remain incompletely understood. DNA interstrand cross-links (ICLs) are among the most cytotoxic type of DNA lesions that block DNA replication and transcription, and these lesions can be induced by endogenous metabolism and by exposure to exogenous agents. Fanconi anemia (FA) is a congenital disorder manifested with elevated sensitivity toward DNA interstrand cross-linking agents...
May 23, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28534493/usp13-negatively-regulates-antiviral-responses-by-deubiquitinating-sting
#4
He Sun, Qiang Zhang, Ying-Ying Jing, Man Zhang, Hai-Ying Wang, Zeng Cai, Tianzi Liuyu, Zhi-Dong Zhang, Tian-Chen Xiong, Yan Wu, Qi-Yun Zhu, Jing Yao, Hong-Bing Shu, Dandan Lin, Bo Zhong
STING (also known as MITA) is critical for host defence against viruses and the activity of STING is regulated by ubiquitination. However, the deubiquitination of STING is not fully understood. Here, we show that ubiquitin-specific protease 13 (USP13) is a STING-interacting protein that catalyses deubiquitination of STING. Knockdown or knockout of USP13 potentiates activation of IRF3 and NF-κB and expression of downstream genes after HSV-1 infection or transfection of DNA ligands. USP13 deficiency results in impaired replication of HSV-1...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28534480/molecular-basis-for-primpol-recruitment-to-replication-forks-by-rpa
#5
Thomas A Guilliam, Nigel C Brissett, Aaron Ehlinger, Benjamin A Keen, Peter Kolesar, Elaine M Taylor, Laura J Bailey, Howard D Lindsay, Walter J Chazin, Aidan J Doherty
DNA damage and secondary structures can stall the replication machinery. Cells possess numerous tolerance mechanisms to complete genome duplication in the presence of such impediments. In addition to translesion synthesis (TLS) polymerases, most eukaryotic cells contain a multifunctional replicative enzyme called primase-polymerase (PrimPol) that is capable of directly bypassing DNA damage by TLS, as well as repriming replication downstream of impediments. Here, we report that PrimPol is recruited to reprime through its interaction with RPA...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28533441/trends-in-dna-methylation-with-age-replicate-across-diverse-human-populations
#6
Shyamalika Gopalan, Oana Carja, Maud Fagny, Etienne Patin, Justin W Myrick, Lisa M McEwen, Sarah M Mah, Michael S Kobor, Alain Froment, Marcus W Feldman, Lluis Quintana-Murci, Brenna M Henn
Aging is associated with widespread changes in genome-wide patterns of DNA methylation. Thousands of CpG sites whose tissue-specific methylation levels are strongly correlated with chronological age have been previously identified. However, the majority of these studies have focused primarily on cosmopolitan populations living in the developed world; it is not known if age-related patterns of DNA methylation at these loci are similar across a broad range of human genetic and ecological diversity. We investigated genome-wide methylation patterns using saliva- and whole blood-derived DNA from two traditionally hunting and gathering African populations: the Baka of the western Central African rainforest and the ≠Khomani San of the South African Kalahari Desert...
May 22, 2017: Genetics
https://www.readbyqxmd.com/read/28533419/dna-replication-and-mismatch-repair-safeguard-against-metabolic-imbalances
#7
Carol M Manhart, Eric Alani
No abstract text is available yet for this article.
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533382/interplay-of-catalysis-fidelity-threading-and-processivity-in-the-exo-and-endonucleolytic-reactions-of-human-exonuclease-i
#8
Yuqian Shi, Homme W Hellinga, Lorena S Beese
Human exonuclease 1 (hExo1) is a member of the RAD2/XPG structure-specific 5'-nuclease superfamily. Its dominant, processive 5'-3' exonuclease and secondary 5'-flap endonuclease activities participate in various DNA repair, recombination, and replication processes. A single active site processes both recessed ends and 5'-flap substrates. By initiating enzyme reactions in crystals, we have trapped hExo1 reaction intermediates that reveal structures of these substrates before and after their exo- and endonucleolytic cleavage, as well as structures of uncleaved, unthreaded, and partially threaded 5' flaps...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28531839/genotoxic-and-mutagenic-effects-of-atrazine-atanor-50-sc-on-dendropsophus-minutus-peters-1872-anura-hylidae-developmental-larval-stages
#9
Macks Wendhell Gonçalves, Calebe Bertolino Marins de Campos, Vinícius Guerra Batista, Aparecido Divino da Cruz, Paulo de Marco Junior, Rogério Pereira Bastos, Daniela de Melo E Silva
The potential mutagenic and genotoxic effects of the herbicide atrazine were investigated in different developmental stages of Dendropsophus minutus tadpoles. These animals were exposed to 4 nominal concentrations of atrazine (2.25, 4.5, 9, and 18 mg/L) and 40 mg/L of Cyclophosphamide as a positive control, for 96 h. Negative controls were also added to the experiment. The tadpoles were divided into three groups according to Gosner's developmental stages, namely GS 25-33 as premetamorphic, GS 36-39 as prometamorphic, and GS 42-43 as metamorphic climax...
May 16, 2017: Chemosphere
https://www.readbyqxmd.com/read/28531327/interstrand-cross-links-arising-from-strand-breaks-at-true-abasic-sites-in-duplex-dna
#10
Zhiyu Yang, Nathan E Price, Kevin M Johnson, Yinsheng Wang, Kent S Gates
Interstrand cross-links are exceptionally bioactive DNA lesions. Endogenous generation of interstrand cross-links in genomic DNA may contribute to aging, neurodegeneration, and cancer. Abasic (Ap) sites are common lesions in genomic DNA that readily undergo spontaneous and amine-catalyzed strand cleavage reactions that generate a 2,3-didehydro-2,3-dideoxyribose sugar remnant (3'ddR5p) at the 3'-terminus of the strand break. Interestingly, this strand scission process leaves an electrophilic α,β-unsaturated aldehyde residue embedded within the resulting nicked duplex...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531315/the-interaction-between-cytosine-methylation-and-processes-of-dna-replication-and-repair-shape-the-mutational-landscape-of-cancer-genomes
#11
Rebecca C Poulos, Jake Olivier, Jason W H Wong
Methylated cytosines (5mCs) are frequently mutated in the genome. However, no studies have yet comprehensively analysed mutation-methylation associations across cancer types. Here we analyse 916 cancer genomes, together with tissue type-specific methylation and replication timing data. We describe a strong mutation-methylation association across colorectal cancer subtypes, most interestingly in samples with microsatellite instability (MSI) or Polymerase epsilon (POLE) exonuclease domain mutations. By analysing genomic regions with differential mismatch repair (MMR) efficiency, we suggest a possible role for MMR in the correction of 5mC deamination events, potentially accounting for the high rate of 5mC mutation accumulation in MSI tumours...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531304/replication-studies-of-carboxymethylated-dna-lesions-in-human-cells
#12
Jun Wu, Pengcheng Wang, Lin Li, Nicole L Williams, Debin Ji, Walter J Zahurancik, Changjun You, Jianshuang Wang, Zucai Suo, Yinsheng Wang
Metabolic activation of some N-nitroso compounds (NOCs), an important class of DNA damaging agents, can induce the carboxymethylation of nucleobases in DNA. Very little was previously known about how the carboxymethylated DNA lesions perturb DNA replication in human cells. Here, we investigated the effects of five carboxymethylated DNA lesions, i.e. O6-CMdG, N6-CMdA, N4-CMdC, N3-CMdT and O4-CMdT on the efficiency and fidelity of DNA replication in HEK293T human embryonic kidney cells. We found that, while neither N6-CMdA nor N4-CMdC blocked DNA replication or induced mutations, N3-CMdT, O4-CMdT and O6-CMdG moderately blocked DNA replication and induced substantial frequencies of T→A (81%), T→C (68%) and G→A (6...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531167/a-role-for-the-host-dna-damage-response-in-hepatitis-b-virus-cccdna-formation-and-beyond
#13
REVIEW
Sabrina Schreiner, Michael Nassal
Chronic hepatitis B virus (HBV) infection puts more than 250 million people at a greatly increased risk to develop end-stage liver disease. Like all hepadnaviruses, HBV replicates via protein-primed reverse transcription of a pregenomic (pg) RNA, yielding an unusually structured, viral polymerase-linked relaxed-circular (RC) DNA as genome in infectious particles. Upon infection, RC-DNA is converted into nuclear covalently closed circular (ccc) DNA. Associating with cellular proteins into an episomal minichromosome, cccDNA acts as template for new viral RNAs, ensuring formation of progeny virions...
May 22, 2017: Viruses
https://www.readbyqxmd.com/read/28530800/label-free-multiplexed-single-molecule-analysis-of-protein-dna-complexes-with-nanopores
#14
Garbiñe Celaya, Judit Perales-Calvo, Arturo Muga, Fernando Moro, David Rodriguez-Larrea
Protein interactions with specific DNA sequences are crucial in the control of gene expression and the regulation of replication. Single-molecule methods offer excellent capabilities to unravel the mechanism and kinetics of these interactions. Here we develop a nanopore approach where a target DNA sequence is contained in a hairpin followed by a ssDNA. This system allows DNA-protein complexes to be distinguished from bare DNA molecules as they are pulled through a single nanopore detector, providing both equilibrium and kinetic information...
May 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/28529930/the-central-role-of-ifi204-in-ifn-%C3%AE-release-and-autophagy-activation-during-mycobacterium-bovis-infection
#15
Liu Chunfa, Sun Xin, Li Qiang, Srinand Sreevatsan, Lifeng Yang, Deming Zhao, Xiangmei Zhou
Mycobacterium bovis (M. bovis) is the pathogen of animals and humans that can replicate in the phagosomes of myeloid cells. Cytosolic detection of bacterial products plays a crucial role in initiating the innate immune response, including autophagy activation and interferon-β (IFN-β) release. Although IFN-β release and autophagy activation have been reported during mycobacterium infection, the mechanisms underlying remains poorly defined. Here, we demonstrated that IFN-β release increases in macrophages exposed to M...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28528978/multimodal-control-of-transcription-factor-pap1-in-schizosaccharomyces-pombe-under-nitrosative-stress
#16
Puranjoy Kar, Pranjal Biswas, Sanjay Ghosh
Schizosaccharomyces pombe Pap1, a bZIP transcription factor, is highly homologous to the mammalian c-Jun protein that belongs to the AP1 family of transcriptional regulators. The role of transcription factor Pap1 has been extensively studied under oxidative stress. Two cysteine residues in Pap1p namely, C278 and C501 form disulfide linkage under oxidative stress resulting in nuclear accumulation. We first time showed the involvement of Pap1 in the protection against nitrosative stress. In the present study we show that pap1 deletion makes growth of S...
May 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28528442/herpesvirus-capsid-assembly-and-dna-packaging
#17
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/28527403/interplay-between-bacillus-subtilis-recd2-and-the-recg-or-ruvab-helicase-in-recombinational-repair
#18
Rubén Torres, Hector Romero, Violeta Rodríguez-Cerrato, Juan C Alonso
Bacillus subtilis AddAB, RecS, RecQ, PcrA, HelD, DinG, RecG, RuvAB, PriA and RecD2 are genuine recombinational repair enzymes, but the biological role of RecD2 is poorly defined. A ΔrecD2 mutation sensitizes cells to DNA-damaging agents that stall or collapse replication forks. We found that this ΔrecD2 mutation impaired growth, and that a mutation in the pcrA gene (pcrA596) relieved this phenotype. The ΔrecD2 mutation was not epistatic to ΔaddAB, ΔrecQ, ΔrecS, ΔhelD, pcrA596 and ΔdinG, but epistatic to recA...
May 12, 2017: DNA Repair
https://www.readbyqxmd.com/read/28526340/unfolding-the-pathogenesis-of-scleroderma-through-genomics-and-epigenomics
#19
REVIEW
Pei-Suen Tsou, Amr H Sawalha
With unknown etiology, scleroderma (SSc) is a multifaceted disease characterized by immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while genetic susceptibility to SSc appears to be modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated...
May 16, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28526201/viral-exploitation-of-the-mek-erk-pathway-a-tale-of-vaccinia-virus-and-other-viruses
#20
REVIEW
Cláudio A Bonjardim
The VACV replication cycle is remarkable in the sense that it is performed entirely in the cytoplasmic compartment of vertebrate cells, due to its capability to encode enzymes required either for regulating the macromolecular precursor pool or the biosynthetic processes. Although remarkable, this gene repertoire is not sufficient to confer the status of a free-living microorganism to the virus, and, consequently, the virus relies heavily on the host to successfully generate its progeny. During the complex virus-host interaction, viruses must deal not only with the host pathways to accomplish their temporal demands but also with pathways that counteract viral infection, including the inflammatory, innate and acquired immune responses...
July 2017: Virology
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