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https://www.readbyqxmd.com/read/29141206/role-of-the-pif1-pcna-complex-in-pol-%C3%AE-dependent-strand-displacement-dna-synthesis-and-break-induced-replication
#1
Olga Buzovetsky, Youngho Kwon, Nhung Tuyet Pham, Claire Kim, Grzegorz Ira, Patrick Sung, Yong Xiong
The S. cerevisiae Pif1 helicase functions with DNA polymerase (Pol) δ in DNA synthesis during break-induced replication (BIR), a conserved pathway responsible for replication fork repair and telomere recombination. Pif1 interacts with the DNA polymerase processivity clamp PCNA, but the functional significance of the Pif1-PCNA complex remains to be elucidated. Here, we solve the crystal structure of PCNA in complex with a non-canonical PCNA-interacting motif in Pif1. The structure guides the construction of a Pif1 mutant that is deficient in PCNA interaction...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29129691/recbcd-exonuclease-v-is-inhibited-by-dna-adducts-produced-by-cisplatin-and-ultraviolet-light
#2
Wai Y Leung, Long H Chung, Hieronimus W Kava, Vincent Murray
The presence of adducts on the DNA double-helix can have major consequences for the efficient functioning of DNA repair enzymes. E. coli RecBCD (exonuclease V) is involved in recombinational repair of double-strand breaks that are caused by defective DNA replication, DNA damaging agents and other factors. The holoenzyme possesses a bipolar helicase activity which helps unwind DNA from both 3'- and 5'-directions and is coupled with a potent exonuclease activity that is also capable of digesting DNA from both 3'- and 5'-ends...
November 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29124702/impact-of-uv-radiation-on-genome-stability-and-human-health
#3
Sujit Roy
Gradual depletion of the atmospheric ozone layer during the past few years has increased the incidence of solar UV radiation specifically the UV-C on earth's surface is one of the major environmental concerns because of the harmful effects of this radiation in all forms of life. The solar UV radiation including the harmful wavelength range of UV-B (280-320 nm) represents a significant climatic stress for both animals and plants, causing damage to the fundamental biomolecules such as DNA, proteins and lipids, thus activating genotoxic stress and induces genome instability...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29121674/the-helicase-ding-responds-to-stress-due-to-dna-double-strand-breaks
#4
Stephan A Frye, Getachew Tesfaye Beyene, Amine Namouchi, Marta Gómez-Muñoz, Håvard Homberset, Shewit Kalayou, Tahira Riaz, Tone Tønjum, Seetha V Balasingham
Neisseria meningitidis (Nm) is a Gram-negative nasopharyngeal commensal that can cause septicaemia and meningitis. The neisserial DNA damage-inducible protein DinG is a helicase related to the mammalian helicases XPD and FANCJ. These helicases belong to superfamily 2, are ATP dependent and exert 5' → 3' directionality. To better understand the role of DinG in neisserial genome maintenance, the Nm DinG (DinGNm) enzymatic activities were assessed in vitro and phenotypical characterization of a dinG null mutant (NmΔdinG) was performed...
2017: PloS One
https://www.readbyqxmd.com/read/29106372/53bp1-and-brca1-control-pathway-choice-for-stalled-replication-restart
#5
Yixi Xu, Shaokai Ning, Zheng Wei, Ran Xu, Xinlin Xu, Mengtan Xing, Rong Guo, Dongyi Xu
The cellular pathways that restart stalled replication forks are essential for genome stability and tumor prevention. However, how many of these pathways exist in cells and how these pathways are selectively activated remain unclear. Here, we describe two major fork restart pathways, and demonstrate that their selection is governed by 53BP1 and BRCA1, which are known to control the pathway choice to repair double-strand DNA breaks (DSBs). Specifically, 53BP1 promotes a fork cleavage-free pathway, whereas BRCA1 facilitates a break-induced replication (BIR) pathway coupled with SLX-MUS complex-mediated fork cleavage...
November 6, 2017: ELife
https://www.readbyqxmd.com/read/29103969/differentiation-of-human-induced-pluripotent-or-embryonic-stem-cells-decreases-the-dna-damage-repair-by-homologous-recombination
#6
Kalpana Mujoo, Raj K Pandita, Anjana Tiwari, Vijay Charaka, Sharmistha Chakraborty, Dharmendra Kumar Singh, Shashank Hambarde, Walter N Hittelman, Nobuo Horikoshi, Clayton R Hunt, Kum Kum Khanna, Alexander Y Kots, E Brian Butler, Ferid Murad, Tej K Pandita
The nitric oxide (NO)-cyclic GMP pathway contributes to human stem cell differentiation, but NO free radical production can also damage DNA, necessitating a robust DNA damage response (DDR) to ensure cell survival. How the DDR is affected by differentiation is unclear. Differentiation of stem cells, either inducible pluripotent or embryonic derived, increased residual DNA damage as determined by γ-H2AX and 53BP1 foci, with increased S-phase-specific chromosomal aberration after exposure to DNA-damaging agents, suggesting reduced homologous recombination (HR) repair as supported by the observation of decreased HR-related repair factor foci formation (RAD51 and BRCA1)...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29093729/an-update-on-the-intracellular-and-intercellular-trafficking-of-carmoviruses
#7
REVIEW
José A Navarro, Vicente Pallás
Despite harboring the smallest genomes among plant RNA viruses, carmoviruses have emerged as an ideal model system for studying essential steps of the viral cycle including intracellular and intercellular trafficking. Two small movement proteins, formerly known as double gene block proteins (DGBp1 and DGBp2), have been involved in the movement throughout the plant of some members of carmovirus genera. DGBp1 RNA-binding capability was indispensable for cell-to-cell movement indicating that viral genomes must interact with DGBp1 to be transported...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29081676/possible-involvement-of-ros-generation-in-vorinostat-pretreatment-induced-enhancement-of-the-antibacterial-activity-of-ciprofloxacin
#8
Majed M Masadeh, Karem H Alzoubi, Sayer I Al-Azzam, Ahlam M Al-Buhairan
The mechanism underlying ciprofloxacin action involves interference with transcription and replication of bacterial DNA and, thus, the induction of double-strand breaks in DNA. It also involves elevated oxidative stress, which might contribute to bacterial cell death. Vorinostat was shown to induce oxidative DNA damage. The current work investigated a possible interactive effect of vorinostat on ciprofloxacin-induced cytotoxicity against a number of reference bacteria. Standard bacterial strains were Escherichia coli ATCC 35218, Staphylococcus aureus ATCC29213, Pseudomonas aeruginosa ATCC 9027, Staphylococcus epidermidis ATCC 12228, Acinetobacter baumannii ATCC 17978, Proteus mirabilis ATCC 12459, Klebsiella pneumoniae ATCC 13883, methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300), and Streptococcus pneumoniae (ATCC 25923)...
2017: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/29061988/aquarius-is-required-for-proper-ctip-expression-and-homologous-recombination-repair
#9
Ryo Sakasai, Mayu Isono, Mitsuo Wakasugi, Mitsumasa Hashimoto, Yumi Sunatani, Tadashi Matsui, Atsushi Shibata, Tsukasa Matsunaga, Kuniyoshi Iwabuchi
Accumulating evidence indicates that transcription is closely related to DNA damage formation and that the loss of RNA biogenesis factors causes genome instability. However, whether such factors are involved in DNA damage responses remains unclear. We focus here on the RNA helicase Aquarius (AQR), a known R-loop processing factor, and show that its depletion in human cells results in the accumulation of DNA damage during S phase, mediated by R-loop formation. We investigated the involvement of Aquarius in DNA damage responses and found that AQR knockdown decreased DNA damage-induced foci formation of Rad51 and replication protein A, suggesting that Aquarius contributes to homologous recombination (HR)-mediated repair of DNA double-strand breaks (DSBs)...
October 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29058747/cobalt-and-nickel-impair-dna-metabolism-by-the-oxidative-stress-independent-pathway
#10
Vineet Kumar, Rajesh Kumar Mishra, Gursharan Kaur, Dipak Dutta
The oxidative stress that evolves under cobalt and nickel exposure is thought to exert toxicity, though the exact routes of such metal poisoning remain ambiguous. We revisited the metal toxicity in Escherichia coli to show that cobalt and nickel exposure at levels as low as 0.5 and 1 mM, respectively, visibly inhibits growth. We also observed that acidic conditions aggravated, while alkaline conditions alleviated the metal toxicity. Besides, 1 mM manganese, which is non-cytotoxic, as judged by the growth of E...
November 15, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29053959/restoration-of-replication-fork-stability-in-brca1-and-brca2-deficient-cells-by-inactivation-of-snf2-family-fork-remodelers
#11
Angelo Taglialatela, Silvia Alvarez, Giuseppe Leuzzi, Vincenzo Sannino, Lepakshi Ranjha, Jen-Wei Huang, Chioma Madubata, Roopesh Anand, Brynn Levy, Raul Rabadan, Petr Cejka, Vincenzo Costanzo, Alberto Ciccia
To ensure the completion of DNA replication and maintenance of genome integrity, DNA repair factors protect stalled replication forks upon replication stress. Previous studies have identified a critical role for the tumor suppressors BRCA1 and BRCA2 in preventing the degradation of nascent DNA by the MRE11 nuclease after replication stress. Here we show that depletion of SMARCAL1, a SNF2-family DNA translocase that remodels stalled forks, restores replication fork stability and reduces the formation of replication stress-induced DNA breaks and chromosomal aberrations in BRCA1/2-deficient cells...
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29043637/assays-to-study-repair-of-inducible-dna-double-strand-breaks-at-telomeres
#12
Roxanne Oshidari, Karim Mekhail
The ends of linear chromosomes are constituted of repetitive DNA sequences called telomeres. Telomeres, nearby regions called subtelomeres, and their associated factors prevent chromosome erosion over cycles of DNA replication and prevent chromosome ends from being recognized as DNA double-strand breaks (DSBs). This raises the question of how cells repair DSBs that actually occur near chromosome ends. One approach is to edit the genome and engineer cells harboring inducible DSB sites within the subtelomeric region of different chromosome ends...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29043623/single-molecule-analysis-of-resection-tracks
#13
Pablo Huertas, Andrés Cruz-García
Homologous recombination is initiated by the so-called DNA end resection, the 5'-3' nucleolytic degradation of a single strand of the DNA at each side of the break. The presence of resected DNA is an obligatory step for homologous recombination. Moreover, the amount of resected DNA modulates the prevalence of different recombination pathways. In different model organisms, there are several published ways to visualize and measure with more or less detail the amount of DNA resected. In human cells, however, technical constraints hampered the study of resection at high resolution...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29042561/aunip-c1orf135-directs-dna-double-strand-breaks-towards-the-homologous-recombination-repair-pathway
#14
Jiangman Lou, Hongxia Chen, Jinhua Han, Hanqing He, Michael S Y Huen, Xin-Hua Feng, Ting Liu, Jun Huang
DNA double-strand breaks (DSBs) are mainly repaired by either homologous recombination (HR) or non-homologous end-joining (NHEJ). Here, we identify AUNIP/C1orf135, a largely uncharacterized protein, as a key determinant of DSB repair pathway choice. AUNIP physically interacts with CtIP and is required for efficient CtIP accumulation at DSBs. AUNIP possesses intrinsic DNA-binding ability with a strong preference for DNA substrates that mimic structures generated at stalled replication forks. This ability to bind DNA is necessary for the recruitment of AUNIP and its binding partner CtIP to DSBs, which in turn drives CtIP-dependent DNA-end resection and HR repair...
October 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29040814/inhibiting-polo-like-kinase-1-plk1-enhances-radiosensitization-via-modulating-dna-repair-proteins-in-non-small-cell-lung-cancer
#15
Da Yao, Peigui Gu, Youyu Wang, Weibin Luo, Huiliang Chi, Jianjun Ge, Youhui Qian
To assure the faithful chromosome segregation, cells make use of the spindle assembly checkpoint (SAC), which can be activated in aneuploidy cancer cells. In this study, the efficacies of inhibiting Polo-like kinase 1 (PLK1) on the radiosensitization of non-small cell lung cancer (NSCLC) cells were studied. Clonogenic survival assay was performed to identify the effects of the PLK1 inhibitor on radiosensitivity within NSCLC cells. Mitotic catastrophe assessment was used to measure the cell death and γH2AX foci were utilized to assess the DNA double-strand breaks (DSB)...
October 17, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29031493/beyond-interstrand-crosslinks-repair-contribution-of-fancd2-and-other-fanconi-anemia-proteins-to-the-replication-of-dna
#16
REVIEW
Maria B Federico, Paola Campodónico, Natalia S Paviolo, Vanesa Gottifredi
Biallelic mutations of FANCD2 and other components of the Fanconi Anemia (FA) pathway cause a disease characterized by bone marrow failure, cancer predisposition and a striking sensitivity to agents that induce crosslinks between the two complementary DNA strands (inter-strand crosslinks-ICL). Such genotoxins were used to characterize the contribution of the FA pathway to the genomic stability of cells, thus unravelling the biological relevance of ICL repair in the context of the disease. Notwithstanding this, whether the defect in ICL repair as the sole trigger for the multiple physiological alterations observed in FA patients is still under investigation...
September 14, 2017: Mutation Research
https://www.readbyqxmd.com/read/29020680/hepatic-t-cell-tolerance-induction-in-an-inflammatory-environment
#17
Janine Dywicki, Fatih Noyan, Ana Clara Misslitz, Martin Hapke, Melanie Galla, Jerome Schlue, Roland S Liblau, Richard Taubert, Michael P Manns, Elmar Jaeckel, Matthias Hardtke-Wolenski
For the development of autoimmune hepatitis (AIH), genetic predisposition and environmental triggers are of major importance. Although experimental AIH can be induced in genetically susceptible mice, the low precursor frequency of autoreactive T cells hampers a deeper analysis of liver-specific T cells. Here, we established a system where the model antigen hemagglutinin (HA) is expressed exclusively in hepatocytes of Rosa26-HA mice following administration of a replication deficient adenovirus expressing Cre recombinase (Ad-Cre)...
October 12, 2017: Digestive Diseases
https://www.readbyqxmd.com/read/28993682/olaparib-modulates-dna-repair-efficiency-sensitizes-cervical-cancer-cells-to-cisplatin-and-exhibits-anti-metastatic-property
#18
Chandra Bhushan Prasad, Shyam Babu Prasad, Suresh Singh Yadav, Laxmi Kant Pandey, Sunita Singh, Satyajit Pradhan, Gopeshwar Narayan
PARP1 trapping at DNA lesion by pharmacological inhibitors has been exploited in several cancers exhibiting defects in DNA repair mechanisms. PARP1 hyperactivation is involved in therapeutic resistance in multiple cancers. The role of PARP1 in cervical cancer (CC) resistance and implication of PARP inhibitor is yet to be elucidated. Our data demonstrates significantly higher expression of PARP1 in primary cervical tumors and CC cell lines SiHa and ME180. Upon cisplatin treatment CC cells display significant overexpression of PARP1 and its hyperactivation...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28983067/increased-loh-due-to-defective-sister-chromatid-cohesion-is-due-primarily-to-chromosomal-aneuploidy-and-not-recombination
#19
Dror Sagi, Evgeniya Marcos-Hadad, Vinay K Bari, Michael A Resnick, Shay Covo
Loss of heterozygosity (LOH) is an important factor in cancer, pathogenic fungi, and adaptation to changing environments. The sister chromatid cohesion process (SCC) suppresses aneuploidy and therefore whole chromosome LOH. SCC is also important to channel recombinational repair to sister chromatids, thereby preventing LOH mediated by allelic recombination. There is, however, insufficient information about the relative roles that the SCC pathway plays in the different modes of LOH. Here, we found that the cohesin mutation mcd1-1, and other mutations in SCC, differentially affect the various types of LOH...
October 5, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28978699/induction-of-dna-damages-upon-marek-s-disease-virus-infection-implication-in-viral-replication-and-pathogenesis
#20
Djihad Bencherit, Sylvie Remy, Yves Le Vern, Tereza Vychodil, Luca D Bertzbach, Benedikt B Kaufer, Caroline Denesvre, Laëtitia Trapp-Fragnet
Marek's disease virus (MDV) is a highly contagious alphaherpesvirus that infects chickens and causes a deadly neoplastic disease. We previously demonstrated that MDV infection arrests cells in S-phase and that the tegument protein VP22 plays a major role in this process. In addition, expression of VP22 induces double strand breaks (DSB) in the cellular DNA, suggesting that DNA damage and the associated cellular response might be favorable for the MDV lifecycle. Here, we addressed the role of DNA damage in MDV replication and pathogenesis...
October 4, 2017: Journal of Virology
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