Abstract:
:Somatic hypermutation (SHM) and class-switch recombination (CSR) of the Ig gene require both the transcription of the locus and the expression of activation-induced cytidine deaminase (AID). During CSR, AID decreases the amount of topoisomerase I (Top1); this decrease alters the DNA structure and induces cleavage in the S region. Similarly, Top1 is involved in transcription-associated mutation at dinucleotide repeats in yeast and in triplet-repeat contraction in mammals. Here, we report that the AID-induced decrease in Top1 is critical for SHM. Top1 knockdown or haploinsufficiency enhanced SHM, whereas Top1 overexpression down-regulated it. A specific Top1 inhibitor, camptothecin, suppressed SHM, indicating that Top1's activity is required for DNA cleavage. Nonetheless, suppression of transcription abolished SHM, even in cells with Top1 knockdown, suggesting that transcription is critical. These results are consistent with a model proposed for CSR and triplet instability, in which transcription-induced non-B structure formation is enhanced by Top1 reduction and provides the target for irreversible cleavage by Top1. We speculate that the mechanism for transcription-coupled genome instability was adopted to generate immune diversity when AID evolved.
journal_name
Proc Natl Acad Sci U S Aauthors
Kobayashi M,Sabouri Z,Sabouri S,Kitawaki Y,Pommier Y,Abe T,Kiyonari H,Honjo Tdoi
10.1073/pnas.1114522108subject
Has Abstractpub_date
2011-11-29 00:00:00pages
19305-10issue
48eissn
0027-8424issn
1091-6490pii
1114522108journal_volume
108pub_type
杂志文章abstract::Resistance to cobalt, zinc, and cadmium specified by the czc determinant on plasmid pMOL30 in Alcaligenes eutrophus results from a cation efflux system. Five membrane-bound polypeptides that were expressed in Escherichia coli from this determinant under the control of a phage T7 promoter were assigned to four open rea...
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.86.19.7351
更新日期:1989-10-01 00:00:00
abstract::The reactivities of N-iodosuccinimide and iodine with various goitrogenic compounds were studied with dimethylsulfoxide through which nitrogen had been bubbled as a solvent. Although iodine does not react with all of the compounds, N-iodosuccinimide does react with all of them. N-Iodosuccinimide may, therefore, serve ...
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.70.5.1401
更新日期:1973-05-01 00:00:00
abstract::C1q-like genes (C1ql1-C1ql4) encode small, secreted proteins that are expressed in differential patterns in the brain but whose receptors and functions remain unknown. BAI3 protein, in contrast, is a member of the cell-adhesion class of G protein-coupled receptors that are expressed at high levels in the brain but who...
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.1019577108
更新日期:2011-02-08 00:00:00
abstract::DNA methylation may be a component of a multilevel control mechanism that regulates eukaryotic gene expression. We used synthetic oligonucleotides to investigate the effect of cytosine methylation on the binding of the transcription factor Sp1 to its target sequence (a G + C-rich sequence known as a "GC box"). Concate...
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.85.7.2066
更新日期:1988-04-01 00:00:00
abstract::Column chromatography on (dT)(12-18)-cellulose was used to detect and isolate a novel DNA polymerase activity from human breast tumor cell line HBT-3. The new enzyme is similar to those of mammalian RNA tumor viruses in its molecular size, preference for poly(A).(dT)(12-18) as compared to either poly(dA).(dT)(12-18) 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.70.8.2453
更新日期:1973-08-01 00:00:00
abstract::The DNA damage response is an essential process for the survival of living cells. In a subset of stress-responsive genes in humans, Elongin controls transcription in response to multiple stimuli, such as DNA damage, oxidative stress, and heat shock. Yeast Elongin (Ela1-Elc1), along with Def1, is known to facilitate ub...
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.1707955114
更新日期:2017-12-12 00:00:00
abstract::The Escherichia coli galactokinase gene (galK) was inserted into a modified early region transcription unit of simian virus 40 (SV40) contained on a bacterial plasmid. Introduction of this pSVK vector into monkey, mouse, and hamster cell lines by transfection resulted in efficient expression of the bacterial galK gene...
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.79.2.257
更新日期:1982-01-01 00:00:00
abstract::MicroRNAs (miRNAs) are endogenously encoded small noncoding RNAs, derived by processing of short RNA hairpins, that can inhibit the translation of mRNAs bearing partially complementary target sequences. In contrast, small interfering RNAs (siRNAs), which are derived by processing of long double-stranded RNAs and are 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.1630797100
更新日期:2003-08-19 00:00:00
abstract::A bone-resorbing factor, comparable to the osteoclast-activating factor (OAF) produced from peripheral blood leukocytes, is shown to be produced by murine spleen cells activated with the T-cell mitogen Con A. Murine OAF is demonstrated here as being a product of the interaction between thymus-derived T lymphocytes and...
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.81.7.2181
更新日期:1984-04-01 00:00:00
abstract::Estrogen receptors (ERs) protect pancreatic islet survival in mice through rapid extranuclear actions. ERalpha also enhances insulin synthesis in cultured islets. Whether ERalpha stimulates insulin synthesis in vivo and, if so, through which mechanism(s) remain largely unknown. To address these issues, we generated 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.0914501107
更新日期:2010-07-20 00:00:00
abstract::A single dose of N-methyl-N-nitrosourea given to sexually immature female Buf/N rats produces a high incidence of mammary adenocarcinomas. A large percentage of these tumors contain the Ha-ras oncogene, activated by a G----A transition at the second nucleotide of codon 12. Copenhagen rats, on the other hand, are compl...
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.89.3.1001
更新日期:1992-02-01 00:00:00
abstract::The heterodisaccharide lactose (1,4-O-beta-D-galactopyranosyl-D-glucose) induces cellulase formation in the ascomycete Hypocrea jecorina (= Trichoderma reesei). Lactose assimilation is slow, and the assimilation of its beta-D-galactose moiety depends mainly on the operation of a recently described reductive pathway an...
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.0802789105
更新日期:2008-05-20 00:00:00
abstract::HLA-G is a nonclassical major histocompatibility complex class I (MHC-I) molecule that is primarily expressed at the fetal-maternal interface, where it is thought to play a role in protecting the fetus from the maternal immune response. HLA-G binds a limited repertoire of peptides and interacts with the inhibitory leu...
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.0409676102
更新日期:2005-03-01 00:00:00
abstract::The imino sugar N-butyldeoxynojirimycin (NBDNJ) is a potent inhibitor of the oligosaccharide-trimming enzyme alpha-glucosidase I. Hepatitis B virus (HBV) contains three surface proteins (HBs proteins) of different sizes that are singly or doubly N-glycosylated and are essential for the formation of infectious virus. 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.91.6.2235
更新日期:1994-03-15 00:00:00
abstract::Blood vessels and nerves often follow parallel trajectories, suggesting that distal targets use common cues that induce vascularization and innervation. Netrins are secreted by the floor plate and attract commissural axons toward the midline of the neural tube. Here, we show that Netrin-1 is also a potent vascular mit...
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.0405984101
更新日期:2004-11-16 00:00:00
abstract::The skeletal muscle sarcoplasmic reticulum (SR) was investigated for the presence of well-known endoplasmic reticulum (ER) markers: the lumenal protein BiP and a group of membrane proteins recognized by an antibody raised against ER membrane vesicles. Western blots of SR fractions revealed the presence of BiP in fast-...
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.89.13.6142
更新日期:1992-07-01 00:00:00
abstract::Cytotactin is an extracellular matrix protein that is dynamically and transiently expressed in a place-dependent fashion during development by glial cells, fibroblasts, and several other cell types. In the present study, the effects of cytotactin on cell proliferation were examined in fibroblastic cells in culture. NI...
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.88.24.11403
更新日期:1991-12-15 00:00:00
abstract::Ca2+-induced inhibition of alpha1C voltage-gated Ca2+ channels is a physiologically important regulatory mechanism that shortens the mean open time of these otherwise long-lasting high-voltage-activated channels. The mechanism of action of Ca2+ has been a matter of some controversy, as previous studies have proposed 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.96.5.2435
更新日期:1999-03-02 00:00:00
abstract::We studied the surface delivery pathways followed by newly synthesized plasma membrane proteins in intestinal cells. To this end, we developed an assay and characterized an epithelial cell line (SK-CO-15) derived from human colon adenocarcinoma. Polarized confluent monolayers (2000 omega.cm2), grown on polycarbonate f...
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.86.23.9313
更新日期:1989-12-01 00:00:00
abstract::DNA methylation is an epigenetic mark that silences transposable elements (TEs) and repeats. Whereas the establishment and maintenance of DNA methylation are relatively well understood, little is known about their dynamics and biological relevance in plant and animal innate immunity. Here, we show that some TEs are de...
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.1211757110
更新日期:2013-02-05 00:00:00
abstract::Treatment of cultured human tumor cells with the chloroethylnitrosourea antitumor drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) selectively induces transcription and protein synthesis of a subset of the human heat shock or stress-induced genes (HSP90 and HSP70) with little effect on other stress genes or on express...
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.88.11.4825
更新日期:1991-06-01 00:00:00
abstract::Some cells from cultured embryonic mouse hypothalamus were found to express aromatic-L-amino acid decarboxylase (EC 4.1.1.28) activity and serotonin uptake and storage. These neuron-like cells differed from serotoninergic neurons in cultured embryonic mouse brain stem since they did not contain tryptophan hydroxylase....
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.83.22.8629
更新日期:1986-11-01 00:00:00
abstract::Current therapeutic interventions for the treatment of respiratory infections are hampered by the evolution of multidrug resistance in pathogens as well as the lack of effective cellular targets. Despite the identification of multiple region-specific lung progenitor cells, the identity of molecules that might be thera...
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.1816030116
更新日期:2019-01-29 00:00:00
abstract::The 8;21 translocation is one of the most common specific rearrangements in acute myelogenous leukemia. We have identified markers (D21S65 and a Not I boundary clone, Not-42, referred to as probe B) flanking the chromosome 21 translocation breakpoint (21q22.3) that demonstrate physical linkage in normal genomic DNA, b...
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.88.11.4882
更新日期:1991-06-01 00:00:00
abstract::X-linked hypophosphatemia is the most prevalent inherited form of rickets. In this disorder, rickets results from hyperphosphaturia and inappropriately normal levels of 1,25(OH)2-vitamin D. Current therapy with oral phosphate and vitamin D improves the rickets, but has significant morbidity and does not significantly ...
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.1834060100
更新日期:2003-09-16 00:00:00
abstract::Methane seeps are widespread seafloor ecosystems shaped by the emission of gas from seabed reservoirs. The microorganisms inhabiting methane seeps transform the chemical energy in methane to products that sustain rich benthic communities around the gas leaks. Despite the biogeochemical relevance of microbial methane 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.1421865112
更新日期:2015-03-31 00:00:00
abstract::The fifth exons of major histocompatibility complex (MHC) class I genes encode a transmembrane domain (TM) that is largely responsible for class I antigen cell-surface expression usually through conventional hydrophobic amino acid-membrane interactions or, less often, through phosphatidylinositol linkage. In this repo...
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.88.11.4666
更新日期:1991-06-01 00:00:00
abstract::Amyloid beta (Aβ) is a major pathological marker in Alzheimer's disease (AD), which is principally regulated by the rate-limiting β-secretase (i.e., BACE1) cleavage of amyloid precursor protein (APP). However, how BACE1 activity is posttranslationally regulated remains incompletely understood. Here, we show that BACE1...
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.1800498115
更新日期:2018-04-10 00:00:00
abstract::In 1950, G. Ledyard Stebbins devoted two chapters of his book Variation and Evolution in Plants (Columbia Univ. Press, New York) to polyploidy, one on occurrence and nature and one on distribution and significance. Fifty years later, many of the questions Stebbins posed have not been answered, and many new questions h...
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.97.13.7051
更新日期:2000-06-20 00:00:00
abstract::For several decades, the iron-based Fenton-like catalysis has been believed to be mediated by hydroxyl radicals or high-valent iron-oxo species, while only sporadic evidence supported the generation of singlet oxygen (1O2) in the Haber-Weiss cycle. Herein, we report an unprecedented singlet oxygen mediated Fenton-like...
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.1819382116
更新日期:2019-04-02 00:00:00