Abstract:
:Oxidation of genomic DNA forms the guanine lesion 7,8-dihydro-8-oxoguanine (8-oxoG). When in the template base position during DNA synthesis the 8-oxoG lesion has dual coding potential by virtue of its anti- and syn-conformations, base pairing with cytosine and adenine, respectively. This impacts mutagenesis, because insertion of adenine opposite template 8-oxoG can result in a G to T transversion. DNA polymerases vary by orders of magnitude in their preferences for mutagenic vs. error-free 8-oxoG lesion bypass. Yet, the structural basis for lesion bypass specificity is not well understood. The DNA base excision repair enzyme DNA polymerase (pol) β is presented with gap-filling synthesis opposite 8-oxoG during repair and has similar insertion efficiencies for dCTP and dATP. We report the structure of pol β in binary complex with template 8-oxoG in a base excision repair substrate. The structure reveals both the syn- and anti-conformations of template 8-oxoG in the confines of the polymerase active site, consistent with the dual coding observed kinetically for this enzyme. A ternary complex structure of pol β with the syn-8-oxoG:anti-A Hoogsteen base pair in the closed fully assembled preinsertion active site is also reported. The syn-conformation of 8-oxoG is stabilized by minor groove hydrogen bonding between the side chain of Arg283 and O8 of 8-oxoG. An adjustment in the position of the phosphodiester backbone 5'-phosphate enables 8-oxoG to adopt the syn-conformation.
journal_name
Proc Natl Acad Sci U S Aauthors
Batra VK,Shock DD,Beard WA,McKenna CE,Wilson SHdoi
10.1073/pnas.1112235108subject
Has Abstractpub_date
2012-01-03 00:00:00pages
113-8issue
1eissn
0027-8424issn
1091-6490pii
1112235108journal_volume
109pub_type
杂志文章abstract::Although the mechanisms of anterior-posterior axis formation are well understood in Drosophila, both embryological and molecular studies suggest significant variation in the mechanisms generating this axis within the Insecta class as a whole. ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.97.9.4442
更新日期:2000-04-25 00:00:00
abstract::Sialic acid-recognizing Ig-like lectins (Siglecs) are signaling receptors that modulate immune responses, and are targeted for interactions by certain pathogens. We describe two primate Siglecs that were rendered nonfunctional by single genetic events during hominin evolution after our common ancestor with the chimpan...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1119459109
更新日期:2012-06-19 00:00:00
abstract::We have found that the bacterial transposon Tn7 can recognize and preferentially insert adjacent to triple-helical nucleic acid structures. Both synthetic intermolecular triplexes, formed through the pairing of a short triplex-forming oligonucleotide on a plasmid DNA, and naturally occurring mirror repeat sequences kn...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.080061497
更新日期:2000-04-11 00:00:00
abstract::Sustained activity of mammalian methionine synthase (MS) requires MS reductase (MSR), but there have been few studies of the interactions between these two proteins. In this study, recombinant human MS (hMS) and MSR (hMSR) were expressed in baculovirus-infected insect cells and purified to homogeneity. hMSR maintained...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0603694103
更新日期:2006-06-20 00:00:00
abstract::In binocular rivalry, a subject views two incongruent stimuli through each eye but consciously perceives only one stimulus at a time, with a switch in perceptual dominance every few seconds. To investigate the neural correlates of perceptual dominance in humans, seven subjects were recorded with a 148-channel magnetoe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.6.3198
更新日期:1998-03-17 00:00:00
abstract::Polyaromatic hydrocarbons are ubiquitous environmental chemicals that are important mutagens and carcinogens. The purpose of this study was to determine whether genes within the major histocompatibility complex (MHC) influence their biological activities. Cell-mediated immunity to dimethylbenz(a)anthracene (DMBA) was ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.25.14915
更新日期:1998-12-08 00:00:00
abstract::It has been controversial whether the cytochrome oxidase (CO)-dense blobs in primate primary visual cortex (V1) and CO-dense thin stripes in visual area 2 (V2) are parts of a cortical color-processing stream that is segregated from other functional streams. One of the key pieces of evidence for the segregated color st...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0402052101
更新日期:2004-05-04 00:00:00
abstract::We have cloned and determined the entire nucleotide sequence of cDNAs corresponding to the putative alpha subunits of the human and rat mast cell high-affinity IgE receptors. Both human and rat cDNAs encode an NH2-terminal signal peptide, two immunoglobulin-like extracellular domains (encoded by discrete exons), a hyd...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.6.1907
更新日期:1988-03-01 00:00:00
abstract::Migration of organisms (or cells) is typically an adaptive response to spatiotemporal variation in resources that requires individuals to detect and respond to long-range and noisy environmental gradients. Many organisms, from wildebeest to bacteria, migrate en masse in a process that can involve a vast number of indi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1006874107
更新日期:2010-09-14 00:00:00
abstract::The two nitrile groups at the wings of the nonnucleoside HIV-1 reverse transcriptase (RT) inhibitor TMC278 are both identified in high-sensitivity 2D IR spectroscopy experiments of the HIV-1 RT/TMC278 complex. The vibrational spectra indicate that the two arms of the inhibitor sense quite different environments within...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0709320104
更新日期:2008-02-05 00:00:00
abstract::Guanylin and uroguanylin are intestinal peptides that stimulate chloride secretion by activating a common set of receptor-guanylate cyclase signaling molecules located on the mucosal surface of enterocytes. High mucosal acidity, similar to the pH occurring within the fluid microclimate domain at the mucosal surface of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.6.2705
更新日期:1997-03-18 00:00:00
abstract::Murine embryonic stem (ES) cells were infected with a retrovirus promoter trap vector, and clones expressing lacZ fusion genes (LacZ+) were isolated by fluorescence-activated cell sorting (FACS). Of 12 fusion genes tested, 1 was repressed when ES cells were allowed to differentiate in vitro. Two of three lacZ fusion g...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.15.6721
更新日期:1992-08-01 00:00:00
abstract::A fundamental problem in cell biology is to understand how spatial information is recognized and integrated into morphogenetic responses. Budding yeast undergoes differentiation to filamentous growth, which involves changes in cell polarity through mechanisms that remain obscure. Here we define a regulatory input wher...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1522679113
更新日期:2016-04-05 00:00:00
abstract::This report describes an unbiased method for systematically determining gene function in mammalian cells. A total of 20,704 predicted human full-length cDNAs were tested for induction of the IL-8 promoter. A number of genes, including those for cytokines, receptors, adapters, kinases, and transcription factors, were i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1932773100
更新日期:2003-10-14 00:00:00
abstract::Jasmonoyl-isoleucine (JA-Ile), the active form of the plant hormone jasmonate (JA), is sensed by the F-box protein CORONATINE INSENSITIVE 1 (COI1), a component of a functional Skp-Cullin-F-box E3 ubiquitin ligase complex. Sensing of JA-Ile by COI1 rapidly triggers genome-wide transcriptional changes that are largely r...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1710885114
更新日期:2017-10-17 00:00:00
abstract::The thrombogenicity of three highly purified proteases (thrombin, activated Factor X, and activated Factor IX) was determined quantitatively in an animal model. The minimal amounts required to produce a standard score 4 thrombus were 1.1 nmol for thrombin, 0.12 nmol for activated Factor X, and 0.018 nmol for activated...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.7.3028
更新日期:1977-07-01 00:00:00
abstract::Cytochrome c peroxidase reacts with peroxide to form compound I, which contains an oxyferryl heme and an indolyl radical at Trp-191. The indolyl free radical has a half-life of several hours at room temperature, and this remarkable stability is essential for the catalytic function of cytochrome c peroxidase. To probe ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.23.11118
更新日期:1994-11-08 00:00:00
abstract::High-performance anion-exchange (HPAE) chromatography under alkaline conditions (pH congruent to 13) has been found to efficiently separate neutral oligosaccharides (triose to undecaose) according to molecular size, sugar composition, and linkage of monosaccharide units. The method was able to resolve 1----3, 1----4, ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.10.3289
更新日期:1988-05-01 00:00:00
abstract::Extensive utilization of pesticides against insects provides us with a good model for studying the adaptation of a eukaryotic genome to a strong selective pressure. One mechanism of resistance is the alteration of acetylcholinesterase (EC 3.1.1.7), the molecular target for organophosphates and carbamates. Here, we rep...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.13.5922
更新日期:1994-06-21 00:00:00
abstract::Many important hominid-bearing fossil localities in East Africa are in regions that are extremely hot and dry. Although humans are well adapted to such conditions, it has been inferred that East African environments were cooler or more wooded during the Pliocene and Pleistocene when this region was a central stage of ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1001824107
更新日期:2010-06-22 00:00:00
abstract::A cylindrical detonating explosive behaves like a non-Newtonian viscous fluid emerging from a cylindrical pipe. The expression for non-Newtonian viscous flow has been applied to detonating explosives. The resultant fit to emerging flame fronts from detonation is excellent for a wide variety of detonating explosives bo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.10.5575
更新日期:1980-10-01 00:00:00
abstract::Finding regions of the genome that are significantly recurrent in noisy data are a common but difficult problem in present day computational biology. Cores of recurrent events (CORE) is a computational approach to solving this problem that is based on a formalized notion by which "core" intervals explain the observed ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1306909110
更新日期:2013-06-18 00:00:00
abstract::During cell division, the mitotic spindle segregates the sister chromatids into two nascent cells, such that each daughter cell inherits one complete set of chromosomes. Errors in spindle formation can result in both chromosome missegregation and cytokinesis defects and hence lead to genomic instability. To ensure the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0507066103
更新日期:2006-04-04 00:00:00
abstract::The goldfish (Carassius auratus) visual pathway displays continuous growth and plasticity throughout life. Since homeobox genes are important transcriptional regulators in development, we searched for homeobox genes in the adult goldfish retina and brain. Using the PCR, we discovered a repertoire of homeobox sequences...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.7.2729
更新日期:1993-04-01 00:00:00
abstract::Multiple drug resistance of tumor cells is a common problem in cancer therapy. We have demonstrated that membrane vesicles from highly multidrug-resistant human KB carcinoma cell lines exhibit increased specific and saturable binding of vinblastine. To identify the molecules that bind vinblastine, membrane vesicles fr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.11.3847
更新日期:1986-06-01 00:00:00
abstract::We have constructed 26-amino acid transmembrane proteins that specifically transform cells but consist of only two different amino acids. Most proteins are long polymers of amino acids with 20 or more chemically distinct side-chains. The artificial transmembrane proteins reported here are the simplest known proteins w...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1514230112
更新日期:2015-08-25 00:00:00
abstract::The three most common methods of sterilization in use today are ethylene oxide exposure, gamma-irradiation, and steam sterilization. Each of these methods has serious limitations for the sterilization of some materials used in medicine, especially thermally and hydrolytically sensitive polymers by themselves and in co...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.18.10344
更新日期:1999-08-31 00:00:00
abstract::An ATP-hydrolyzing activity with the properties of a Mg(2+)-dependent (Na(+),K(+))-ATPase (ATP phosphohydrolase, EC 3.6.1.3) from a 20-fold purified plasma membrane fraction of the marine diatom, Nitzschia alba is described. The basal activity requires Mg(2+) and further stimulation by Na(+) or Na(+) plus K(+) is depe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.71.11.4376
更新日期:1974-11-01 00:00:00
abstract::Bordetella pertussis secretes a calmodulin-activated adenylate cyclase toxin, CyaA, that is able to deliver its N-terminal catalytic domain (400-aa residues) into the cytosol of eukaryotic target cells, directly through the cytoplasmic membrane. We have previously shown that CyaA can be used as a vehicle to deliver T ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.21.12532
更新日期:1998-10-13 00:00:00
abstract::Although melanomas with mutant v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) can now be effectively targeted, there is no molecular target for most melanomas expressing wild-type BRAF. Here, we show that the activation of Pleckstrin homology domain-interacting protein (PHIP), promotes melanoma metastasis, can ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1119949109
更新日期:2012-05-01 00:00:00