Single-molecule imaging reveals target-search mechanisms during DNA mismatch repair.

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.

authors

Gorman J,Wang F,Redding S,Plys AJ,Fazio T,Wind S,Alani EE,Greene EC

doi

10.1073/pnas.1211364109

subject

Has Abstract

pub_date

2012-11-06 00:00:00

pages

E3074-83

issue

45

eissn

0027-8424

issn

1091-6490

pii

1211364109

journal_volume

109

pub_type

杂志文章
  • The neural development and organization of letter recognition: evidence from functional neuroimaging, computational modeling, and behavioral studies.

    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

    authors: Polk TA,Farah MJ

    更新日期:1998-02-03 00:00:00

  • Quantitative determination of transformed cells in a mixed population by stimultaneous fluorescence analysis of cell surface and DNA an individual cells.

    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

    authors: Hawkes SP,Bartholomew JC

    更新日期:1977-04-01 00:00:00

  • Intracellular disruption of rat heart lysosomes by leucine methyl ester: effects on protein degradation.

    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

    authors: Reeves JP,Decker RS,Crie JS,Wildenthal K

    更新日期:1981-07-01 00:00:00

  • Early-life stress has persistent effects on amygdala function and development in mice and humans.

    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

    authors: Malter Cohen M,Jing D,Yang RR,Tottenham N,Lee FS,Casey BJ

    更新日期:2013-11-05 00:00:00

  • Mathematical modeling elucidates the role of transcriptional feedback in gibberellin signaling.

    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

    authors: Middleton AM,Úbeda-Tomás S,Griffiths J,Holman T,Hedden P,Thomas SG,Phillips AL,Holdsworth MJ,Bennett MJ,King JR,Owen MR

    更新日期:2012-05-08 00:00:00

  • An engineered innate immune defense protects grapevines from Pierce disease.

    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

    authors: Dandekar AM,Gouran H,Ibáñez AM,Uratsu SL,Agüero CB,McFarland S,Borhani Y,Feldstein PA,Bruening G,Nascimento R,Goulart LR,Pardington PE,Chaudhary A,Norvell M,Civerolo E,Gupta G

    更新日期:2012-03-06 00:00:00

  • Plant genomics: more than food for thought.

    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

    authors: Briggs SP

    更新日期:1998-03-03 00:00:00

  • Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury.

    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

    authors: Zhu L,Bergmeier W,Wu J,Jiang H,Stalker TJ,Cieslak M,Fan R,Boumsell L,Kumanogoh A,Kikutani H,Tamagnone L,Wagner DD,Milla ME,Brass LF

    更新日期:2007-01-30 00:00:00

  • Sphingosine-dependent apoptosis: a unified concept based on multiple mechanisms operating in concert.

    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

    authors: Suzuki E,Handa K,Toledo MS,Hakomori S

    更新日期:2004-10-12 00:00:00

  • An adenovirus type 5 early gene function regulates expression of other early viral genes.

    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

    authors: Jones N,Shenk T

    更新日期:1979-08-01 00:00:00

  • Opportunistic pathogens enriched in showerhead biofilms.

    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

    authors: Feazel LM,Baumgartner LK,Peterson KL,Frank DN,Harris JK,Pace NR

    更新日期:2009-09-22 00:00:00

  • Conserved mechanism of cell-wall synthase regulation revealed by the identification of a new PBP activator in Pseudomonas aeruginosa.

    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

    authors: Greene NG,Fumeaux C,Bernhardt TG

    更新日期:2018-03-20 00:00:00

  • Replication infidelity during a single cycle of Ty1 retrotransposition.

    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

    authors: Gabriel A,Willems M,Mules EH,Boeke JD

    更新日期:1996-07-23 00:00:00

  • Higher offspring survival among Tibetan women with high oxygen saturation genotypes residing at 4,000 m.

    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

    authors: Beall CM,Song K,Elston RC,Goldstein MC

    更新日期:2004-09-28 00:00:00

  • Pervasive CpG suppression in animal mitochondrial genomes.

    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

    authors: Cardon LR,Burge C,Clayton DA,Karlin S

    更新日期:1994-04-26 00:00:00

  • Comparative homology agreement search: an effective combination of homology-search methods.

    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

    authors: Alam I,Dress A,Rehmsmeier M,Fuellen G

    更新日期:2004-09-21 00:00:00

  • TOM1, an Arabidopsis gene required for efficient multiplication of a tobamovirus, encodes a putative transmembrane protein.

    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

    authors: Yamanaka T,Ohta T,Takahashi M,Meshi T,Schmidt R,Dean C,Naito S,Ishikawa M

    更新日期:2000-08-29 00:00:00

  • Genomic drift and copy number variation of sensory receptor genes in humans.

    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

    authors: Nozawa M,Kawahara Y,Nei M

    更新日期:2007-12-18 00:00:00

  • SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling.

    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

    authors: Tang J,Sawasdikosol S,Chang JH,Burakoff SJ

    更新日期:1999-08-17 00:00:00

  • Ammonia-oxidizing archaea use the most energy-efficient aerobic pathway for CO2 fixation.

    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

    authors: Könneke M,Schubert DM,Brown PC,Hügler M,Standfest S,Schwander T,Schada von Borzyskowski L,Erb TJ,Stahl DA,Berg IA

    更新日期:2014-06-03 00:00:00

  • Single protein from human leukocytes possesses 5-lipoxygenase and leukotriene A4 synthase activities.

    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

    authors: Rouzer CA,Matsumoto T,Samuelsson B

    更新日期:1986-02-01 00:00:00

  • Primary structure of the gamma-carboxyglutamic acid-containing protein from bovine bone.

    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

    authors: Price PA,Poser JW,Raman N

    更新日期:1976-10-01 00:00:00

  • Carbon dioxide fixation as a central redox cofactor recycling mechanism in bacteria.

    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

    authors: McKinlay JB,Harwood CS

    更新日期:2010-06-29 00:00:00

  • Inheritance of Trans Chromosomal Methylation patterns from Arabidopsis F1 hybrids.

    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

    authors: Greaves IK,Groszmann M,Wang A,Peacock WJ,Dennis ES

    更新日期:2014-02-04 00:00:00

  • Differential olivo-cerebellar cortical control of rebound activity in the cerebellar nuclei.

    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

    authors: Hoebeek FE,Witter L,Ruigrok TJ,De Zeeuw CI

    更新日期:2010-05-04 00:00:00

  • Structural evidence that human liver and placental alkaline phosphatase isoenzymes are coded by different genes.

    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

    authors: Badger KS,Sussman HH

    更新日期:1976-07-01 00:00:00

  • Molecular determinants of the modulation of cyclic nucleotide-activated channels by calmodulin.

    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

    authors: Grunwald ME,Zhong H,Lai J,Yau KW

    更新日期:1999-11-09 00:00:00

  • Metachromatic leukodystrophy: arylsulfatase-A deficiency in skin fibroblast cultures.

    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

    authors: Porter MT,Fluharty AL,Kihara H

    更新日期:1969-03-01 00:00:00

  • Small mitochondrial Arf (smArf) protein corrects p53-independent developmental defects of Arf tumor suppressor-deficient mice.

    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

    authors: van Oosterwijk JG,Li C,Yang X,Opferman JT,Sherr CJ

    更新日期:2017-07-11 00:00:00

  • Ultraconserved words point to deep language ancestry across Eurasia.

    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

    authors: Pagel M,Atkinson QD,S Calude A,Meade A

    更新日期:2013-05-21 00:00:00