Abstract:
:The ability of proteins to locate specific targets among a vast excess of nonspecific DNA is a fundamental theme in biology. Basic principles governing these search mechanisms remain poorly understood, and no study has provided direct visualization of single proteins searching for and engaging target sites. Here we use the postreplicative mismatch repair proteins MutSα and MutLα as model systems for understanding diffusion-based target searches. Using single-molecule microscopy, we directly visualize MutSα as it searches for DNA lesions, MutLα as it searches for lesion-bound MutSα, and the MutSα/MutLα complex as it scans the flanking DNA. We also show that MutLα undergoes intersite transfer between juxtaposed DNA segments while searching for lesion-bound MutSα, but this activity is suppressed upon association with MutSα, ensuring that MutS/MutL remains associated with the damage-bearing strand while scanning the flanking DNA. Our findings highlight a hierarchy of lesion- and ATP-dependent transitions involving both MutSα and MutLα, and help establish how different modes of diffusion can be used during recognition and repair of damaged DNA.
journal_name
Proc Natl Acad Sci U S Aauthors
Gorman J,Wang F,Redding S,Plys AJ,Fazio T,Wind S,Alani EE,Greene ECdoi
10.1073/pnas.1211364109subject
Has Abstractpub_date
2012-11-06 00:00:00pages
E3074-83issue
45eissn
0027-8424issn
1091-6490pii
1211364109journal_volume
109pub_type
杂志文章abstract::Although much of the brain's functional organization is genetically predetermined, it appears that some noninnate functions can come to depend on dedicated and segregated neural tissue. In this paper, we describe a series of experiments that have investigated the neural development and organization of one such noninna...
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.95.3.847
更新日期:1998-02-03 00:00:00
abstract::Cell-surface labeling with fluorescamine indicates that the fluorescence of Balb 3T3 A31 cells in considerably decreased after both viral and chemical transformation. This phenomenon, coupled with the technique of flow microfluorometry, enabled nontransformed and transformed cells to be distinguished. A second fluroes...
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.74.4.1626
更新日期:1977-04-01 00:00:00
abstract::Perfusion of rat hearts with Krebs--Henseleit medium containing 10 mM L-leucine methyl ester leads to swelling of lysosomes and loss of lysosomal integrity within 30-60 min. No morphological changes can be detected in the nuclei, mitochondria, sarcoplasmic reticulum, or Golgi complex as a result of the treatment with ...
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.78.7.4426
更新日期:1981-07-01 00:00:00
abstract::Relatively little is known about neurobiological changes attributable to early-life stressors (e.g., orphanage rearing), even though they have been associated with a heightened risk for later psychopathology. Human neuroimaging and animal studies provide complementary insights into the neural basis of problem behavior...
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.1310163110
更新日期:2013-11-05 00:00:00
abstract::The hormone gibberellin (GA) is a key regulator of plant growth. Many of the components of the gibberellin signal transduction [e.g., GIBBERELLIN INSENSITIVE DWARF 1 (GID1) and DELLA], biosynthesis [e.g., GA 20-oxidase (GA20ox) and GA3ox], and deactivation pathways have been identified. Gibberellin binds its receptor,...
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.1113666109
更新日期:2012-05-08 00:00:00
abstract::We postulated that a synergistic combination of two innate immune functions, pathogen surface recognition and lysis, in a protein chimera would lead to a robust class of engineered antimicrobial therapeutics for protection against pathogens. In support of our hypothesis, we have engineered such a chimera to protect ag...
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.1116027109
更新日期:2012-03-06 00:00:00
abstract::In all but the poorest countries of South Asia and Africa, the supply and quality of food will rise to meet the demand. Biotechnology, accelerated by genomics, will create wealth for both producers and consumers by reducing the cost and increasing the quality of food. Famine and malnutrition in the poorest countries m...
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.95.5.1986
更新日期:1998-03-03 00:00:00
abstract::Semaphorin 4D (sema4D; CD100) is an integral membrane protein and the ligand for two receptors, CD72 and plexin-B1. Soluble sema4D has been shown to evoke angiogenic responses from endothelial cells and impair monocyte migration, but the origin of soluble sema4D, particularly at sites of vascular injury, has been uncl...
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.0606344104
更新日期:2007-01-30 00:00:00
abstract::Exposure of 3T3/A31 cells to serum-free medium, one type of apoptotic stimulus, causes a rapid increase in the sphingosine (Sph) level, which initiates a series of processes: (i) activation of caspase 3 through an enhanced "cascade" of caspases, (ii) release of the C-terminal-half kinase domain of PKCdelta (PKCdelta K...
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.0406536101
更新日期:2004-10-12 00:00:00
abstract::We have identified an adenovirus type 5(Ad5) early gene function located in early region 1 which is required for the production of early cytoplasmic mRNAs corresponding to early regions 2, 3, and 4. Mutant dl312 (lacks the segment between 1.5 and 4.5 map units) grows as well as wild-type virus in 293 cells (Ad5-trans...
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.76.8.3665
更新日期:1979-08-01 00:00:00
abstract::The environments we humans encounter daily are sources of exposure to diverse microbial communities, some of potential concern to human health. In this study, we used culture-independent technology to investigate the microbial composition of biofilms inside showerheads as ecological assemblages in the human indoor env...
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.0908446106
更新日期:2009-09-22 00:00:00
abstract::Penicillin-binding proteins (PBPs) are synthases required to build the essential peptidoglycan (PG) cell wall surrounding most bacterial cells. The mechanisms regulating the activity of these enzymes to control PG synthesis remain surprisingly poorly defined given their status as key antibiotic targets. Several years ...
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.1717925115
更新日期:2018-03-20 00:00:00
abstract::Retroviruses undergo a high frequency of genetic alterations during the process of copying their RNA genomes. However, little is known about the replication fidelity of other elements that transpose via reverse transcription of an RNA intermediate. The complete sequence of 29 independently integrated copies of the yea...
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.93.15.7767
更新日期:1996-07-23 00:00:00
abstract::Here we test the hypothesis that high-altitude native resident Tibetan women with genotypes for high oxygen saturation of hemoglobin, and thus less physiological hypoxic stress, have higher Darwinian fitness than women with low oxygen saturation genotypes. Oxygen saturation and genealogical data were collected from re...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,多中心研究
doi:10.1073/pnas.0405949101
更新日期:2004-09-28 00:00:00
abstract::All available complete mitochondrial genomes (21 species) are evaluated for dinucleotide over- and under-representation. The CpG dinucleotide is pervasively under-represented in all animal mitochondria, but it is of variable relative abundance in fungal, protist, and plant mitochondrial genomes. Interpretations and hy...
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.91.9.3799
更新日期:1994-04-26 00:00:00
abstract::Many methods have been developed to search for homologous members of a protein family in databases, and the reliability of results and conclusions may be compromised if only one method is used, neglecting the others. Here we introduce a general scheme for combining such methods. Based on this scheme, we implemented a ...
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.0405612101
更新日期:2004-09-21 00:00:00
abstract::Host-encoded factors play an important role in virus multiplication, acting in concert with virus-encoded factors. However, information regarding the host factors involved in this process is limited. Here we report the map-based cloning of an Arabidopsis thaliana gene, TOM1, which is necessary for the efficient multip...
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.170295097
更新日期:2000-08-29 00:00:00
abstract::The number of sensory receptor genes varies extensively among different mammalian species. This variation is believed to be caused partly by physiological requirements of animals and partly by genomic drift due to random duplication and deletion of genes. If the contribution of genomic drift is substantial, each speci...
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.0709956104
更新日期:2007-12-18 00:00:00
abstract::Engagement of the T cell antigen receptor (TCR) leads to rapid activation of protein tyrosine kinases, which in turn phosphorylate downstream enzymes and adapter proteins. Some adapter proteins, such as SLP-76, Vav, and LAT, positively regulate TCR-mediated signal transduction, whereas others, such as Cbl, play an inh...
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.96.17.9775
更新日期:1999-08-17 00:00:00
abstract::Archaea of the phylum Thaumarchaeota are among the most abundant prokaryotes on Earth and are widely distributed in marine, terrestrial, and geothermal environments. All studied Thaumarchaeota couple the oxidation of ammonia at extremely low concentrations with carbon fixation. As the predominant nitrifiers in the oce...
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.1402028111
更新日期:2014-06-03 00:00:00
abstract::The activity of leukotriene A4 (LTA4) synthase in crude human leukocyte homogenates was found to have a similar requirement for Ca2+ and ATP as had been noted previously for 5-lipoxygenase activity. Purification of the 5-lipoxygenase using ammonium sulfate fractionation, AcA 44 gel-filtration chromatography, and HPLC ...
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.83.4.857
更新日期:1986-02-01 00:00:00
abstract::The amino-acid sequence of the gamma-carboxyglutamic acid-containing protein of bovine bone is presented. The sequence of 43 of the 49 residues was determined automatically on the intact protein and on a tryptic peptide. The remainder was determined by conventional procedures on tryptic and chymotrytic peptides. Resid...
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.73.10.3374
更新日期:1976-10-01 00:00:00
abstract::The Calvin-Benson-Bassham cycle (Calvin cycle) catalyzes virtually all primary productivity on Earth and is the major sink for atmospheric CO(2). A less appreciated function of CO(2) fixation is as an electron-accepting process. It is known that anoxygenic phototrophic bacteria require the Calvin cycle to accept elect...
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.1006175107
更新日期:2010-06-29 00:00:00
abstract::Hybridization in plants leads to transinteractions between the parental genomes and epigenomes that can result in changes to both 24 nt siRNA and cytosine methylation ((m)C) levels in the hybrid. In Arabidopsis the principle processes altering the hybrid methylome are Trans Chromosomal Methylation (TCM) and Trans Chro...
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.1323656111
更新日期:2014-02-04 00:00:00
abstract::The output of the cerebellar cortex is controlled by two main inputs, (i.e., the climbing fiber and mossy fiber-parallel fiber pathway) and activations of these inputs elicit characteristic effects in its Purkinje cells: that is, the so-called complex spikes and simple spikes. Target neurons of the Purkinje cells in 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.0907118107
更新日期:2010-05-04 00:00:00
abstract::Human liver alkaline phosphatase [ortho-phosphoric monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] was purified, and some of its physical and chemical properties were examined and compared to those of human placental alkaline phosphatase. The results indicated a different peptide structure for each, based u...
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.73.7.2201
更新日期:1976-07-01 00:00:00
abstract::The action of calmodulin (CaM) on target proteins is important for a variety of cellular functions. We demonstrate here, however, that the presence of a CaM-binding site on a protein does not necessarily imply a functional effect. The alpha-subunit of the cGMP-gated cation channel of human retinal cones has a CaM-bind...
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.96.23.13444
更新日期:1999-11-09 00:00:00
abstract::Fibroblasts cultured from the skin of a patient with metachromatic leukodystrophy have been found to manifest the biochemical defect of this inborn error of metabolism, a deficiency of arylsulfatase A. Diseased cells had less than five per cent of normal arylsulfatase-A activity, while activities of other lysosomal en...
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.62.3.887
更新日期:1969-03-01 00:00:00
abstract::The mouse p19Arf (human p14ARF) tumor suppressor protein, encoded in part from an alternative reading frame of the Ink4a (Cdkn2a) gene, inhibits the Mdm2 E3 ubiquitin ligase to activate p53. Arf is not expressed in most normal tissues of young mice but is induced by high thresholds of aberrant hyperproliferative signa...
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.1707292114
更新日期:2017-07-11 00:00:00
abstract::The search for ever deeper relationships among the World's languages is bedeviled by the fact that most words evolve too rapidly to preserve evidence of their ancestry beyond 5,000 to 9,000 y. On the other hand, quantitative modeling indicates that some "ultraconserved" words exist that might be used to find evidence ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.1218726110
更新日期:2013-05-21 00:00:00