Abstract:
:Activation-induced cytidine deaminase (AID) is essential to class-switch recombination (CSR) and somatic hypermutation (SHM) in both V region SHM and S region SHM (s-SHM). Uracil DNA glycosylase (UNG), a member of the base excision repair (BER) complex, is required for CSR. Strikingly, however, UNG deficiency causes augmentation of SHM, suggesting involvement of distinct functions of UNG in SHM and CSR. Here, we show that noncanonical scaffold functions of UNG regulate s-SHM negatively and CSR positively. The s-SHM suppressive function of UNG is attributed to the recruitment of faithful BER components at the cleaved DNA locus, with competition against error-prone polymerases. By contrast, the CSR-promoting function of UNG enhances AID-dependent S-S synapse formation by recruiting p53-binding protein 1 and DNA-dependent protein kinase, catalytic subunit. Several loss-of-catalysis mutants of UNG discriminated CSR-promoting activity from s-SHM suppressive activity. Taken together, the noncanonical function of UNG regulates the steps after AID-induced DNA cleavage: error-prone repair suppression in s-SHM and end-joining promotion in CSR.
journal_name
Proc Natl Acad Sci U S Aauthors
Yousif AS,Stanlie A,Mondal S,Honjo T,Begum NAdoi
10.1073/pnas.1402391111subject
Has Abstractpub_date
2014-03-18 00:00:00pages
E1016-24issue
11eissn
0027-8424issn
1091-6490pii
1402391111journal_volume
111pub_type
杂志文章abstract::Message passing is a fundamental technique for performing calculations on networks and graphs with applications in physics, computer science, statistics, and machine learning, including Bayesian inference, spin models, satisfiability, graph partitioning, network epidemiology, and the calculation of matrix eigenvalues....
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.1914893116
更新日期:2019-11-19 00:00:00
abstract::Peripheral nerve injury induces a robust proregenerative program that drives axon regeneration. While many regeneration-associated genes are known, the mechanisms by which injury activates them are less well-understood. To identify such mechanisms, we performed a loss-of-function pharmacological screen in cultured adu...
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.1805351115
更新日期:2018-10-16 00:00:00
abstract::Small, single-module proteins that fold in a single cooperative step may be paradigms for understanding early events in protein-folding pathways generally. Recent experimental studies of the 64-residue chymotrypsin inhibitor 2 (CI2) support a nucleation mechanism for folding, as do some computer stimulations. CI2 has ...
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.92.24.10869
更新日期:1995-11-21 00:00:00
abstract::Three distinct endosomal fractions were isolated in high purity from livers of estradiol-treated rats. Each fraction had characteristic physical and ultrastructural properties, but the lipid composition and major proteins of their membranes were similar and differed from those derived from the Golgi apparatus. Injecte...
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.84.19.6785
更新日期:1987-10-01 00:00:00
abstract::The bacterial RsgA, a circularly permutated GTPase, whose GTPase activity is dependent on the 30S ribosomal subunit, is a late-stage ribosome biogenesis factor involved in the 30S subunit maturation. The role of RsgA is to release another 30S biogenesis factor, RbfA, from the mature 30S subunit in a GTP-dependent mann...
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.1104645108
更新日期:2011-08-09 00:00:00
abstract::The assembly of tiny magnetic particles in external magnetic fields is important for many applications ranging from data storage to medical technologies. The development of ever smaller magnetic structures is restricted by a size limit, where the particles are just barely magnetic. For such particles we report the dis...
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.1511443112
更新日期:2015-11-24 00:00:00
abstract::An amine-functionalized derivative of 1,3-dipropyl-8-phenylxanthine has been prepared in tritiated form as a xanthine amine congener ([3H]XAC) for use as an antagonist radioligand for adenosine receptors. [3H]XAC has higher receptor affinity, higher specific activity, lower nonspecific membrane binding, and more favor...
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.83.11.4089
更新日期:1986-06-01 00:00:00
abstract::To examine the influence of interferon gamma (IFN-gamma) on tumorigenicity, we established constitutively IFN-gamma-producing cell lines from a malignant mouse neuroblastoma, C1300, by retroviral transfer of a mouse IFN-gamma cDNA. The gene-transferred cells generally showed an enhanced high-level expression of the ma...
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.86.23.9456
更新日期:1989-12-01 00:00:00
abstract::The counterintuitive features of quantum physics challenge many common-sense assumptions. In an interferometric quantum eraser experiment, one can actively choose whether or not to erase which-path information (a particle feature) of one quantum system and thus observe its wave feature via interference or not by perfo...
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.1213201110
更新日期:2013-01-22 00:00:00
abstract::We describe a system for gene expression in plants based on the regulation mechanism of the yeast metallothionein (MT) gene. The system consists of two elements: (i) the yeast ace1 (activating copper-MT expression) gene encoding a transcription factor under control of the cauliflower mosaic virus (CaMV) 35S RNA promot...
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.90.10.4567
更新日期:1993-05-15 00:00:00
abstract::Lactobacillus johnsonii NCC 533 is a member of the acidophilus group of intestinal lactobacilli that has been extensively studied for their "probiotic" activities that include, pathogen inhibition, epithelial cell attachment, and immunomodulation. To gain insight into its physiology and identify genes potentially invo...
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.0307327101
更新日期:2004-02-24 00:00:00
abstract::An isoform of the mammalian renal type II Na/Pi-cotransporter is described. Homology of this isoform to described mammalian and nonmammalian type II cotransporters is between 57 and 75%. Based on major diversities at the C terminus, the new isoform is designed as type IIb Na/Pi-cotransporter. Na/Pi-cotransport mediate...
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.95.24.14564
更新日期:1998-11-24 00:00:00
abstract::Hox genes encode transcription factors that control spatial patterning during embryogenesis. To date, downstream targets of Hox genes have proven difficult to identify. Here, we describe studies designed to identify target genes under the control of the murine transcription factor Hoxc8. We used a mouse 16,463 gene ol...
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.0409700102
更新日期:2005-02-15 00:00:00
abstract::Autoimmunity often involves the abnormal targeting of self-antigens by antibodies, leading to tissue destruction and other pathologies. This process could potentially be disrupted by small ligands that bind specifically to autoantibodies and inhibit their interaction with the target antigen. Here we report the identif...
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.92.6.2355
更新日期:1995-03-14 00:00:00
abstract::Various tissues and cells in culture contain a specific inhibitor of DNase I (EC 3.1.4.5). In this paper evidence is presented that this inhibitor is actin, one of the major structural proteins of muscle and nonmuscle cells. (a) The inhibitor is a major cellular component constituting 5-10% of the soluble protein. (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.71.12.4742
更新日期:1974-12-01 00:00:00
abstract::The trace fossil record is important in determining the timing of the appearance of bilaterian animals. A conservative estimate puts this time at approximately equal 555 million years ago. The preservational potential of traces made close to the sediment-water interface is crucial to detecting early benthic activity. ...
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.202322499
更新日期:2002-10-01 00:00:00
abstract::DBA/2 mice immunized with poly(A).poly(U) complexed with methylated bovine serum albumin and emulsified in Freund's complete adjuvant were protected against challenge with Friend leukemia virus. There was no correlation between the level of antibody to the immunogen in the prechallenge serum and induced resistance to ...
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.76.4.2018
更新日期:1979-04-01 00:00:00
abstract::Direct structural insights on the fundamental mechanisms of permeation, selectivity, and gating remain unavailable for the Na(+) and Ca(2+) channel families. Here, we report the spectroscopic structural characterization of the isolated Voltage-Sensor Domain (VSD) of the prokaryotic Na(+) channel NaChBac in a lipid bil...
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.0914109107
更新日期:2010-03-23 00:00:00
abstract::We have cloned two species of EcoRI-cleaved DNA segments that together cover the entire sequence for the human interleukin 2 gene and have determined the nucleotide sequence of the gene and its flanking regions. The gene contains three introns and the exon sequences can be aligned with the previously reported cDNA seq...
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.80.24.7437
更新日期:1983-12-01 00:00:00
abstract::Highly pathogenic avian influenza A viruses of subtypes H5 and H7 are the causative agents of fowl plague in poultry. Influenza A viruses of subtype H5N1 also caused severe respiratory disease in humans in Hong Kong in 1997 and 2003, including at least seven fatal cases, posing a serious human pandemic threat. Between...
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.0308352100
更新日期:2004-02-03 00:00:00
abstract::An automatic protein design procedure is used to select amino acid sequences that optimize the folding free energy function for a given protein. The only information used in designing the sequences is a set of known backbone structures for each protein, a rotamer library, and a well established classical empirical 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.212068599
更新日期:2002-10-15 00:00:00
abstract::We know a great deal about the cellular response to starvation via AMPK, but less is known about the reaction to nutrient excess. Insulin resistance may be an appropriate response to nutrient excess, but the cellular sensors that link these parameters remain poorly defined. In the present study we provide evidence tha...
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.0902380106
更新日期:2009-10-20 00:00:00
abstract::Herpesvirus extracted from a naturally occurring frog renal carcinoma (Lucké tumor) induced virus-free Lucké tumors in developing frogs. Herpesvirus recovered from an induced tumor after incubation at low temperature of tumor fragments cultured in vitro was oncogenic when injected into developing frog embryos. With th...
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.71.3.830
更新日期:1974-03-01 00:00:00
abstract::Tumor necrosis factor alpha (TNF-alpha), also known as cachectin, was demonstrated to induce the expression of human immunodeficiency virus (HIV) in a chronically infected T-cell clone (ACH-2). Concentrations of recombinant TNF-alpha as low as 50 pg/ml induced a significant increase over background of HIV expression 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.86.7.2365
更新日期:1989-04-01 00:00:00
abstract::Familial multiple system tauopathy with presenile dementia (MSTD) is a neurodegenerative disease with an abundant filamentous tau protein pathology. It belongs to the group of familial frontotemporal dementias with Parkinsonism linked to chromosome 17 (FTDP-17), a major class of inherited dementing disorders whose gen...
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.95.13.7737
更新日期:1998-06-23 00:00:00
abstract::beta1,4-Galactosyltransferase (beta4GalT-I) participates in both glycoconjugate biosynthesis (ubiquitous activity) and lactose biosynthesis (mammary gland-specific activity). In somatic tissues, transcription of the mammalian beta4GalT-I gene results in a 4.1-kb mRNA and a 3.9-kb mRNA as a consequence of initiation at...
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.95.25.14805
更新日期:1998-12-08 00:00:00
abstract::Pre-mRNA splicing requires the bridging of the 5' and 3' ends of the intron. In yeast, this bridging involves interactions between the WW domains in the splicing factor PRP40 and a proline-rich domain in the branchpoint binding protein, BBP. Using a proline-rich domain derived from formin (a product of the murine limb...
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.95.18.10602
更新日期:1998-09-01 00:00:00
abstract::The values of the moment of inertia of the ground-state band of (168)Hf from J = 0(+) to 22(+) are interpreted as involving a revolving cluster with composition increasing steadily from p(10.5)n(14) to p(20.5)n(24), with radius of revolution 6.390 fm. The excited bands from 14(+) to 34(+), 21(-) to 33(-), and 18(-) to...
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.81.10.3261
更新日期:1984-05-01 00:00:00
abstract::Arsenic has played a key medicinal role against a variety of ailments for several millennia, but during the past century its prominence has been displaced by modern therapeutics. Recently, attention has been drawn to arsenic by its dramatic clinical efficacy against acute promyelocytic leukemia. Although toxic reactiv...
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.0306687101
更新日期:2004-03-30 00:00:00
abstract::Anthrax toxin is an intracellularly acting toxin in which sufficient information is available regarding the structure of its transmembrane channel, allowing for detailed investigation of models of translocation. Anthrax toxin, comprising three proteins-protective antigen (PA), lethal factor (LF), and edema factor-tran...
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.1600624113
更新日期:2016-08-23 00:00:00