Abstract:
:All cells are unavoidably exposed to chemicals that can alkylate DNA to form genotoxic damage. Among the various DNA lesions formed, O(6)-alkylguanine lesions can be highly cytotoxic, and we recently demonstrated that O(6)-methylguanine (O(6)MeG) and O(6)-chloroethylguanine (O(6)CEG) specifically initiate apoptosis in hamster cells. Here we show, in both hamster and human cells, that the MutSalpha branch of the DNA mismatch repair pathway (but not the MutSbeta branch) is absolutely required for signaling the initiation of apoptosis in response to O(6)MeGs and is partially required for signaling apoptosis in response to O(6)CEGs. Further, O(6)MeG lesions signal the stabilization of the p53 tumor suppressor, and such signaling is also MutSalpha-dependent. Despite this, MutSalpha-dependent apoptosis can be executed in a p53-independent manner. DNA mismatch repair status did not influence the response of cells to other inducers of p53 and apoptosis. Thus, it appears that mismatch repair status, rather than p53 status, is a strong indicator of the susceptibility of cells to alkylation-induced apoptosis. This experimental system will allow dissection of the signal transduction events that couple a specific type of DNA base lesion with the final outcome of apoptotic cell death.
journal_name
Proc Natl Acad Sci U S Aauthors
Hickman MJ,Samson LDdoi
10.1073/pnas.96.19.10764keywords:
subject
Has Abstractpub_date
1999-09-14 00:00:00pages
10764-9issue
19eissn
0027-8424issn
1091-6490journal_volume
96pub_type
杂志文章abstract::The number of x-irradiated mammalian cells surviving is markedly increased when the cells are incubated with an uncoupler of oxidative phosphorylation prior to or immediately after irradiation. This increase is greater in plateau-phase cells than in exponentially growing cells. The increase in survival is related to 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.77.5.2702
更新日期:1980-05-01 00:00:00
abstract::N6-methyladenosine (m6A) represents one of the most common RNA modifications in eukaryotes. Specific m6A writer, eraser, and reader proteins have been identified. As an m6A eraser, ALKBH5 specifically removes m6A from target mRNAs and inactivation of Alkbh5 leads to male infertility in mice. However, the underlying mo...
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.1717794115
更新日期:2018-01-09 00:00:00
abstract::Salivary gland cells in the larvae of the dipteran Chironomus tentans offer unique possibilities to visualize the assembly and nucleocytoplasmic transport of a specific transcription product. Each nucleus harbors four giant polytene chromosomes, whose transcription sites are expanded, or puffed. On chromosome IV, ther...
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.111145498
更新日期:2001-06-19 00:00:00
abstract::Muscle contraction and relaxation is regulated by transient elevations of myoplasmic Ca(2+). Ca(2+) is released from stores in the lumen of the sarco(endo)plasmic reticulum (SER) to initiate formation of the Ca(2+) transient by activation of a class of Ca(2+) release channels referred to as ryanodine receptors (RyRs) ...
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.0905186106
更新日期:2009-07-07 00:00:00
abstract::A single intravenous (i.v.) injection of the water-soluble mammary carcinogen N-nitroso-N-methylurea (NMU; 35 mg/kg of body weight) elicited cancer of the breast in young female rats of two strains in the following incidence: Long-Evans strain, 4%; Sprague-Dawley strain, 70%. In sisters of these rats, a set of 5 i.v. ...
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.78.2.1185
更新日期:1981-02-01 00:00:00
abstract::Analysis of the activity and structure of lower vertebrate alcohol dehydrogenases reveals that relationships between the classical liver and yeast enzymes need not be continuous. Both the ethanol activity of class I-type alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) and the glutathione-dependent form...
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.89.19.9247
更新日期:1992-10-01 00:00:00
abstract::Cyanobacteria, blue-green algae, are the most abundant autotrophs in aquatic environments and form the base of all aquatic food chains by fixing carbon and nitrogen into cellular biomass. The single most important nutrient for photosynthesis and growth is nitrate, which is severely limiting in many aquatic environment...
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.0602517103
更新日期:2006-06-27 00:00:00
abstract::The neural crest (NC) emerges from combinatorial inductive events occurring within its progenitor domain, the neural border (NB). Several transcription factors act early at the NB, but the initiating molecular events remain elusive. Recent data from basal vertebrates suggest that ap2 might have been critical for NC em...
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.1010740107
更新日期:2011-01-04 00:00:00
abstract::Copper is a required metal nutrient for life, but global or local alterations in its homeostasis are linked to diseases spanning genetic and metabolic disorders to cancer and neurodegeneration. Technologies that enable longitudinal in vivo monitoring of dynamic copper pools can help meet the need to study the complex ...
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.1613628113
更新日期:2016-12-13 00:00:00
abstract::The self assembly of phospholipid molecules in the bilayer form was considered in terms of equivalent molecular shapes representing intermolecular forces. The equivalent size of each phospholipid headgroup was approximated by the net atomic volume plus the volume of the associated water molecules, which was derived 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.86.15.5825
更新日期:1989-08-01 00:00:00
abstract::Effects of thyrotropin-releasing hormone (TRH; thyroliberin) on membrane electrical properties were studied in the clonal rat anterior pituitary cell (GH3) by continuous recording of the intracellular potential. Application of TRH, which stimulates the release of prolactin and growth hormone from the GH3 cell, elicite...
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.76.11.6017
更新日期:1979-11-01 00:00:00
abstract::The principal sequence feature responsible for intrinsic DNA curvature is generally assumed to be runs of adenines. However, according to the wedge model of DNA curvature, each dinucleotide step is associated with a characteristic deflection of the local helix axis. Thus, an important test of a more general view of se...
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.88.6.2312
更新日期:1991-03-15 00:00:00
abstract::Several nonclassical major histocompatibilty antigens (class Ib molecules) have emerged as key players in the early immune response to pathogens or stress. Class Ib molecules activate subsets of T cells that mount effector responses before the adaptive immune system, and thus are called innate T cells. MR1 is a novel ...
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.0903196106
更新日期:2009-05-19 00:00:00
abstract::Among the earliest and most important stages during tumorigenesis is the activation of the angiogenic process, an event that is termed the "switch to the angiogenic phenotype." We have developed an in vivo system that can reliably recapitulate the stages in tumor development that represent this transition. Using this ...
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.97.8.3884
更新日期:2000-04-11 00:00:00
abstract::ADP activates a family of cell surface receptors that modulate signaling pathways in a broad range of cells. ADP receptor antagonists are widely used to treat cardiovascular disease states. These studies identify a critical role for the stable reactive oxygen species hydrogen peroxide (H2O2) in mediating cellular resp...
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.1320854111
更新日期:2014-03-04 00:00:00
abstract::Staphylococcus aureus is a leading cause of both nosocomial and community-acquired infection. Biofilm formation at the site of infection reduces antimicrobial susceptibility and can lead to chronic infection. During biofilm formation, a subset of cells liberate cytoplasmic proteins and DNA, which are repurposed to for...
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.1704544114
更新日期:2017-07-18 00:00:00
abstract::Morphogenesis often yields organs with robust size and shapes, whereas cell growth and deformation feature significant spatiotemporal variability. Here, we investigate whether tissue responses to mechanical signals contribute to resolve this apparent paradox. We built a model of growing tissue made of fiber-like mater...
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.1815342116
更新日期:2019-02-05 00:00:00
abstract::Breast cancers show variable sensitivity to paclitaxel. There is no diagnostic test to identify tumors that are sensitive to this drug. We used U133A chips to identify genes that are associated with pathologic complete response (pCR) to preoperative paclitaxel-containing chemotherapy in stage I-III breast cancer (n = ...
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.0408974102
更新日期:2005-06-07 00:00:00
abstract::The sloppy paired (slp) locus consists of two genes, slp1 and slp2, both of which encode proteins containing a forkhead domain (a DNA-binding motif). Previous work has shown that a severe segmentation phenotype is obtained only when both slp genes are deleted. Here we examine the functional redundancy of the locus in ...
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.91.14.6324
更新日期:1994-07-05 00:00:00
abstract::Fluorescence of quinacrine in the presence of different polynucleotides was studied to attempt to identify the specific nucleotides responsible for the fluorescence of stained chromosome preparations. A marked enhancement of fluorescence was seen in the presence of bihelical polynucleotides, such as poly(dA-dT), poly(...
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.69.3.629
更新日期:1972-03-01 00:00:00
abstract::Increasing concentrations of estradiol (E2) ranging from 0.01 to 10 nM were found to inhibit partially but significantly the lactogenic effect of ovine prolactin (oPRL) on alpha-lactalbumin production in primate mammary tissues maintained in organ culture for 9 days. E2 at 10 nM inhibited by 38% (mean) PRL-stimulated ...
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.80.13.4144
更新日期:1983-07-01 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::We describe the molecular cloning of various DNA segments generated by partial EcoRI endonuclease digestion of the sex factor F. These segments have been analyzed by agarose gel electrophoresis of EcoRI digests and were arranged in a series of overlapping fragments using the EcoRI fragment map of F established by H. O...
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.73.1.64
更新日期:1976-01-01 00:00:00
abstract::The neuroactive steroids dehydroepiandrosterone (DHEA), its sulfate ester DHEA sulfate (DHEAS), and allopregnanolone (Allo), produced by the CNS and the adrenals, appear to exert a protective effect in hippocampal and cortical neuron ischemia- and excitotoxicity-induced injury. We hypothesized that they may also play ...
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.0306631101
更新日期:2004-05-25 00:00:00
abstract::The transthyretin amyloidoses (ATTR) are invariably fatal diseases characterized by progressive neuropathy and/or cardiomyopathy. ATTR are caused by aggregation of transthyretin (TTR), a natively tetrameric protein involved in the transport of thyroxine and the vitamin A-retinol-binding protein complex. Mutations 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.1121005109
更新日期:2012-06-12 00:00:00
abstract::The unicellular green alga Chlamydomonas swims with two flagella that can synchronize their beat. Synchronized beating is required to swim both fast and straight. A long-standing hypothesis proposes that synchronization of flagella results from hydrodynamic coupling, but the details are not understood. Here, we presen...
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.1300895110
更新日期:2013-11-05 00:00:00
abstract::Helper T (Th) cells are classified as Th1 or Th2 cells by virtue of cytokine secretion and function as mediators of cellular or humoral immunity, respectively. Cytokines also regulate the differentiation of Th cells. For example, interleukin (IL)-12 promotes Th1 and suppresses Th2 cell development, suggesting that IL-...
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.92.15.6847
更新日期:1995-07-18 00:00:00
abstract::High-resolution crystal structures of editing complexes of both duplex and single-stranded DNA bound to Escherichia coli DNA polymerase I large fragment (Klenow fragment) show four nucleotides of single-stranded DNA bound to the 3'-5' exonuclease active site and extending toward the polymerase active site. Melting 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.85.23.8924
更新日期:1988-12-01 00:00:00
abstract::A 320-base-pair repeated sequence was observed when DNA samples from the filarial parasites Brugia malayi and Brugia pahangi were digested with the restriction endonuclease Hha I. A 640-base-pair dimer of the repeated sequence from B. malayi was inserted into the plasmid pBR322. When dot hybridization was used, the 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.83.3.797
更新日期:1986-02-01 00:00:00
abstract::By using a structure-based computer-assisted search, we have found a butyrophenone derivative that is a selective inhibitor of the human immunodeficiency virus 1 (HIV-1) protease. The computer program creates a negative image of the active site cavity using the crystal structure of the HIV-1 protease. This image was c...
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.87.17.6644
更新日期:1990-09-01 00:00:00