DNA damage

Autophagy and DNA repair are two essential biological mechanisms that maintain cellular homeostasis. Impairment of these mechanisms was associated with several pathologies such as premature aging, neurodegenerative diseases, and cancer. Intrinsic or extrinsic stress stimuli (e.g., reactive oxygen species or ionizing radiation) cause DNA damage. As a biological stress response, autophagy is activated following insults that threaten DNA integrity.

18p thiencuuchu 27-11-2021 11 1   Download

Theoxidation-promotingreactivityof copper(II) complexof aminoglycosidic antibiotic amikacin [Cu(II)-Ami] in the presence of hydrogen peroxide, was studied at pH 7.4, using 2¢-deoxyguanosine (dG), pBR322 plasmid DNA and yeast tRNA Phe as target molecules. Themixtures of complexwith H2O2were found to be efficient oxidants, converting dG to its 8-oxo derivative, generating strand breaks in plasmid DNA and multiple cleavages in tRNA Phe .

10p tumor12 22-04-2013 35 3   Download

Formamidopyrimidine-DNA glycosylase (Fpg protein) of Escherichia coliis a DNA repair enzyme that excises oxi-dized purine bases, most notably the mutagenic 7-hydro-8-oxoguanine, from damaged DNA. In order to identify specific contacts between nucleobases of DNA and amino acids from theE. coliFpg protein, photochemical cross-linking was employed using new reactive DNA duplexes containing 5-[4-[3-(trifluoromethyl)-3H-diazirin-3-yl]phe-nyl]-2¢-deoxyuridine dU* residues near the 7-hydro-8-oxoguanosine (oxoG) lesion. ...

5p fptmusic 16-04-2013 31 3   Download

We have previously reported that sulfoquinovosylmonoacylglycerol (SQMG) is a potent inhibitor of mammalian DNA polymerases. DNA polymeraseb(pol b) is one of the most important enzymes protecting the cell against DNA damage by base excision repair. In this study, we charac-terized the inhibitory action of SQMG against rat pol b. SQMG competed with both the substrate and the template-primer for binding to polb.

13p fptmusic 11-04-2013 40 1   Download

DNA repair must take place within the context of chromatin, and it is therefore not surprising that many aspects of both chromatin components and proteins that modify chromatin have been implicated in this process. One of the best-characterized chromatin modification events in DNA-dam-age responses is the phosphorylation of the SQ motif found in histone H2A or the H2AX histone variant in higher eukaryotes. This modification is an early response to the induction of DNA damage, and occurs in a wide range of eukaryotic organisms, suggesting an important conserved func-tion....

10p fptmusic 11-04-2013 22 1   Download

Base excision repair (BER), a major pathway for the removal of simple lesions in DNA, requires the co-ordinated action of several repair and ancillary proteins, the impairment of which can lead to genetic instability. We here address the role of poly(ADP-ribose) polymerase-1 (PARP-1) in BER. Using anin vitro cross-linking assay, we reveal that PARP-1 is always involved in repair of a uracil-containing oligonucleotide and that it binds to the damaged DNA during the early stages of repair.

0p awards 06-04-2013 43 2   Download

Phosphorylation at multiple sites within the N-terminus of p53 promotes its dissociation from hdm2/mdm2 and sti-mulates its transcriptional regulatory potential. The large phosphoinositide 3-kinase-like kinases ataxia telangiectasia mutated gene product and the ataxia telangectasia and RAD-3-related kinase promote phosphorylation of human p53at Ser15andSer20, andare required for theactivationof p53 following DNA damage.

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Ionizing radiation, oxidative stress and endogenous DNA-damage pro-cessing can result in a variety of single-strand breaks with modified 5¢ and⁄or 3¢ ends. These are thought to be one of the most persistent forms of DNA damage and may threaten cell survival. This study addresses the mechanism involved in recognition and processing of DNA strand breaks containing modified 3¢ ends.

11p dell39 27-03-2013 60 6   Download

The Nbs1 protein associates with Mre11 and Rad50 proteins to form the Mre11–Rad50–Nbs1 complex, which plays an important role in the intracellular signaling pathway activated in response to DNA damage. Mutations in the genes for each of these three components of the Mre11– Rad50–Nbs1 complex result in human diseases characterized by genomic instability.

7p inspiron33 26-03-2013 53 4   Download

Xeroderma pigmentosum (XP) is an inherited disease in which cells from patients exhibit defects in nucleotide excision repair (NER). XP proteins A–G are crucial in the processes of DNA damage recognition and incision, and patients with XP can carry mutations in any of the genes that specify these proteins.

9p inspiron33 26-03-2013 51 6   Download

We investigated the survival signals of epidermal growth factor (EGF) in human gastric adenocarcinoma cell line TMK-1. Treatment of TMK-1 cells with adriamycin (ADR) caused apoptosis and apoptosis-related reactions such as the release of cytochromecfrom mitochondria and the activation of caspase 9.

13p inspiron33 25-03-2013 42 2   Download

DNA-binding proteins from starved cells (Dps proteins) protect bacteria primarily from oxidative damage. They are composed of 12 identical subunits assembled with 23-symmetry to form a compact cage-like struc-ture known to be stable at temperatures 70C and over a wide pH range. Thermosynechococcus elongatus Dps thermostability is increased dramatically relative to mesophilic Dps proteins.

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Cell survival depends not only on the ability to repair damaged DNA but also on the capability to perform DNA replication on unrepaired or imperfect templates. Crucial to this process are specialized DNA polym-erases belonging to the Y family. These enzymes share a similar catalytic fold in their N-terminal region, and most of them have a less-well-con-served C-terminus which is not required for catalytic activity.

11p galaxyss3 19-03-2013 36 3   Download

Cisplatin (cis-diamminedichloroplatinum) and related chemotherapeutic DNA-crosslinking agents are widely used to treat human cancers.Saccha-romyces cerevisiae with separate deletions of the genes encoding the trimeric protein serine⁄threonine phosphatase (Pph)3p–platinum sensitivity (Psy)4p–Psy2p complex, are more sensitive than the isogenic wild-type (WT) strain to cisplatin.

11p galaxyss3 07-03-2013 38 3   Download

Pyruvate is located at a crucial crossroad of cellular metabolism between the aerobic and anaerobic pathways. Modulation of the fate of pyruvate, in one direction or another, can be important for adaptative response to hypoxia followed by reoxygenation.

11p media19 04-03-2013 40 3   Download

Hypoxic preconditioning may afford protection against subsequent lethal hypoxia. As hypoxic tolerance induces changes in the expression of genes involved in DNA damage and repair response pathways, we investigated whether DNA-dependent protein kinase (DNA-PK), one of the DNA dou-ble-strand break repair proteins, could be involved in hypoxic precondi-tioning-induced protective signaling cascades.

13p vinaphone15 28-02-2013 41 4   Download

Human 8-oxoguanine-DNA glycosylase (OGG1) efficiently removes muta-genic 8-oxo-7,8-dihydroguanine (8-oxoGua) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine when paired with cytosine in oxidatively damaged DNA. Excision of 8-oxoGua mispaired with adenine may lead to GfiT transversions.

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Cockayne syndrome (CS) is a complex, progressive disease that involves neurological and developmental impairment and premature aging. The majority of CS patients have mutations in theCSBgene. The CSB protein is involved in multiple DNA repair pathways and CSBmutated cells are sensitive to a broad spectrum of genotoxic agents.

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Genomic stability is constantly threatened by DNA damage, caused by numerous environmental and intrinsic sources, including radiation, chemi-cals and oncogene expression. Consequently, cells have evolved a sophisti-cated signal transduction network to sense DNA damage and to mount an appropriate DNA damage response.

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Mutations in the tumor suppressor breast cancer susceptibility gene 1 (BRCA1), an important player in the DNA damage response, apoptosis, cell cycle regulation and transcription, confer a significantly elevated life-time risk for breast and ovarian cancer.

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