Different mutation signatures in DNA polymerase eta- and MSH6-deficient mice suggest separate roles in antibody diversification.

Abstract:

:Hypermutation in immunoglobulin genes produces a high frequency of substitutions of all four bases, which are likely generated by low-fidelity DNA polymerases. Indeed, humans deficient for DNA polymerase (pol) eta have decreased substitutions of A.T base pairs in variable and switch regions. To study the role of pol eta in a genetically tractable system, we created mice lacking pol eta. B cells from Polh-/- mice produced normal amounts of IgG, indicating that pol eta does not affect class switch recombination. Similar to their human counterparts, variable and switch regions from Polh-/- mice had fewer substitutions of A.T base pairs and correspondingly more mutations of C.G base pairs, which firmly establishes a central role for pol eta in hypermutation. Notably, the location and types of substitutions differ markedly from those in Msh6-/- clones, which also have fewer A.T mutations. The data suggest that pol eta preferentially synthesizes a repair patch on the nontranscribed strand, whereas MSH6 functions to generate the patch.

authors

Martomo SA,Yang WW,Wersto RP,Ohkumo T,Kondo Y,Yokoi M,Masutani C,Hanaoka F,Gearhart PJ

doi

10.1073/pnas.0501852102

keywords:

subject

Has Abstract

pub_date

2005-06-14 00:00:00

pages

8656-61

issue

24

eissn

0027-8424

issn

1091-6490

pii

0501852102

journal_volume

102

pub_type

杂志文章
  • Online purchasing creates opportunities to lower the life cycle carbon footprints of consumer products.

    abstract::A major barrier to transitions to environmental sustainability is that consumers lack information about the full environmental footprints of their purchases. Sellers' incentives do not support reducing the footprints unless customers have such information and are willing to act on it. We explore the potential of moder...

    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.1522211113

    authors: Isley SC,Stern PC,Carmichael SP,Joseph KM,Arent DJ

    更新日期:2016-08-30 00:00:00

  • Monomeric and trimeric forms of photosystem I reaction center of Mastigocladus laminosus: crystallization and preliminary characterization.

    abstract::Photosystem I (PSI) reaction centers (RCs) of the thermophilic cyanobacterium Mastigocladus laminosus were purified and characterized. The PSI RC was obtained in two forms, monomeric and trimeric. The two forms contained the same number of pigments per P700 and displayed similar photochemical activities. The two forms...

    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.88.12.5312

    authors: Almog O,Shoham G,Michaeli D,Nechushtai R

    更新日期:1991-06-15 00:00:00

  • Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita.

    abstract::Dyskeratosis congenita is a rare inherited disorder characterized by abnormal skin manifestations. Morbidity and mortality from this disease is usually due to bone marrow failure, but idiopathic pulmonary fibrosis and an increased cancer predisposition also occur. Families with autosomal dominant dyskeratosis congenit...

    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.0508124102

    authors: Armanios M,Chen JL,Chang YP,Brodsky RA,Hawkins A,Griffin CA,Eshleman JR,Cohen AR,Chakravarti A,Hamosh A,Greider CW

    更新日期:2005-11-01 00:00:00

  • Dynamics and elasticity of the fibronectin matrix in living cell culture visualized by fibronectin-green fluorescent protein.

    abstract::Fibronectin (FN) forms the primitive fibrillar matrix in both embryos and healing wounds. To study the matrix in living cell cultures, we have constructed a cell line that secretes FN molecules chimeric with green fluorescent protein. These FN-green fluorescent protein molecules were assembled into a typical matrix 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.96.5.2153

    authors: Ohashi T,Kiehart DP,Erickson HP

    更新日期:1999-03-02 00:00:00

  • The human brain is intrinsically organized into dynamic, anticorrelated functional networks.

    abstract::During performance of attention-demanding cognitive tasks, certain regions of the brain routinely increase activity, whereas others routinely decrease activity. In this study, we investigate the extent to which this task-related dichotomy is represented intrinsically in the resting human brain through examination of s...

    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.0504136102

    authors: Fox MD,Snyder AZ,Vincent JL,Corbetta M,Van Essen DC,Raichle ME

    更新日期:2005-07-05 00:00:00

  • Expression and functional significance of VE-cadherin in aggressive human melanoma cells: role in vasculogenic mimicry.

    abstract::We recently have introduced the term vasculogenic mimicry to describe the unique ability of aggressive melanoma tumor cells to form tubular structures and patterned networks in three-dimensional culture, which "mimics" embryonic vasculogenic networks formed by differentiating endothelial cells. In the current study, w...

    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.131209798

    authors: Hendrix MJ,Seftor EA,Meltzer PS,Gardner LM,Hess AR,Kirschmann DA,Schatteman GC,Seftor RE

    更新日期:2001-07-03 00:00:00

  • Probable extirpation of a breeding colony of Short-tailed Albatross (Phoebastria albatrus) on Bermuda by Pleistocene sea-level rise.

    abstract::Albatrosses (Diomedeidae) do not occur in the North Atlantic Ocean today except as vagrants, although five species were present in the early Pliocene. No fossil breeding sites of albatrosses were known previously. The timing of extinction of albatrosses in the North Atlantic was likewise unknown. Deposits that formed ...

    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.1934576100

    authors: Olson SL,Hearty PJ

    更新日期:2003-10-28 00:00:00

  • Early regional specification for a molecular neuronal phenotype in the rat neocortex.

    abstract::The timing of neocortical regional specification was examined using a monoclonal antibody, designated PC3.1, that binds a 29-kDa polypeptide and recognizes a neuronal subpopulation located in the lateral but not dorsomedial neocortex in the rat. When lateral cortical tissue fragments at embryonic days 12 and 16 were 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.89.19.8879

    authors: Arimatsu Y,Miyamoto M,Nihonmatsu I,Hirata K,Uratani Y,Hatanaka Y,Takiguchi-Hayashi K

    更新日期:1992-10-01 00:00:00

  • Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Δ32 mutation confers resistance to HIV infection.

    abstract::Individuals homozygous for the C-C chemokine receptor type 5 gene with 32-bp deletions (CCR5Δ32) are resistant to HIV-1 infection. In this study, we generated induced pluripotent stem cells (iPSCs) homozygous for the naturally occurring CCR5Δ32 mutation through genome editing of wild-type iPSCs using a combination 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.1407473111

    authors: Ye L,Wang J,Beyer AI,Teque F,Cradick TJ,Qi Z,Chang JC,Bao G,Muench MO,Yu J,Levy JA,Kan YW

    更新日期:2014-07-01 00:00:00

  • Crystal structure of MICU2 and comparison with MICU1 reveal insights into the uniporter gating mechanism.

    abstract::The mitochondrial uniporter is a Ca2+-channel complex resident within the organelle's inner membrane. In mammalian cells the uniporter's activity is regulated by Ca2+ due to concerted action of MICU1 and MICU2, two paralogous, but functionally distinct, EF-hand Ca2+-binding proteins. Here we present the X-ray structur...

    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.1817759116

    authors: Kamer KJ,Jiang W,Kaushik VK,Mootha VK,Grabarek Z

    更新日期:2019-02-26 00:00:00

  • Characterization of Mbb1, a nucleus-encoded tetratricopeptide-like repeat protein required for expression of the chloroplast psbB/psbT/psbH gene cluster in Chlamydomonas reinhardtii.

    abstract::Genetic analysis has revealed that the accumulation of several chloroplast mRNAs of the green alga Chlamydomonas reinhardtii requires specific nucleus-encoded functions. To gain insight into this process, we have cloned the nuclear gene encoding the Mbb1 factor by genomic rescue of a mutant specifically deficient 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.97.26.14813

    authors: Vaistij FE,Boudreau E,Lemaire SD,Goldschmidt-Clermont M,Rochaix JD

    更新日期:2000-12-19 00:00:00

  • Interaction of the Wiskott-Aldrich syndrome protein with sorting nexin 9 is required for CD28 endocytosis and cosignaling in T cells.

    abstract::The Wiskott-Aldrich syndrome protein (WASp) plays a major role in coupling T cell antigen receptor (TCR) stimulation to induction of actin cytoskeletal changes required for T cell activation. Here, we report that WASp inducibly binds the sorting nexin 9 (SNX9) in T cells and that WASp, SNX9, p85, and CD28 colocalize w...

    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.0610543104

    authors: Badour K,McGavin MK,Zhang J,Freeman S,Vieira C,Filipp D,Julius M,Mills GB,Siminovitch KA

    更新日期:2007-01-30 00:00:00

  • Homeostatic mechanisms regulate distinct aspects of cortical circuit dynamics.

    abstract::Homeostasis is indispensable to counteract the destabilizing effects of Hebbian plasticity. Although it is commonly assumed that homeostasis modulates synaptic strength, membrane excitability, and firing rates, its role at the neural circuit and network level is unknown. Here, we identify changes in higher-order netwo...

    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.1918368117

    authors: Wu YK,Hengen KB,Turrigiano GG,Gjorgjieva J

    更新日期:2020-09-29 00:00:00

  • Concerted biosynthesis of an insect elicitor of plant volatiles.

    abstract::A variety of agricultural plant species, including corn, respond to insect herbivore damage by releasing large quantities of volatile compounds and, as a result, become highly attractive to parasitic wasps that attack the herbivores. An elicitor of plant volatiles, N-(17-hydroxylinolenoyl)-L-glutamine, named volicitin...

    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.95.23.13971

    authors: Paré PW,Alborn HT,Tumlinson JH

    更新日期:1998-11-10 00:00:00

  • Mortality invariants and their genetic implications.

    abstract::Old noninbred fly mortality decreases according to the inverse linear law and reduces to a single suborder-specific age. Relative child mortality (the mortality at a given age related to the mortality at 10 years) from 1 mo to 11 years is the same with 8% mean accuracy for all humans, independent of race, country, sex...

    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.95.15.9037

    authors: Azbel' MY

    更新日期:1998-07-21 00:00:00

  • Folding free energy function selects native-like protein sequences in the core but not on the surface.

    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

    authors: Jaramillo A,Wernisch L,Héry S,Wodak SJ

    更新日期:2002-10-15 00:00:00

  • In vivo functional protein-protein interaction: nuclear targeted hsp90 shifts cytoplasmic steroid receptor mutants into the nucleus.

    abstract::In target tissue extracts, heat shock protein hsp90 has been found associated to all unliganded steroid receptors. Modulation of important functions of these receptors, including prevention of DNA binding and optimization of transcriptional activity, has been attributed to hsp90. However no unequivocal in vivo demonst...

    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.91.1.340

    authors: Kang KI,Devin J,Cadepond F,Jibard N,Guiochon-Mantel A,Baulieu EE,Catelli MG

    更新日期:1994-01-04 00:00:00

  • Clathrin-immunoreactive sites in the Golgi apparatus are concentrated at the trans pole in polypeptide hormone-secreting cells.

    abstract::By analogy with receptor-mediated endocytosis, clathrin-coated membrane segments at locations other than at the plasma membrane have been implicated in intracellular membrane transport/sorting. The crucial role of the Golgi apparatus in these processes prompted us to study the distribution at this level of clathrin-im...

    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.82.16.5385

    authors: Orci L,Ravazzola M,Amherdt M,Louvard D,Perrelet A

    更新日期:1985-08-01 00:00:00

  • CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines.

    abstract::CD28 is a 44-kDa glycoprotein expressed as a homodimer on the surface of a major subset of human T cells. Previous studies have demonstrated that the binding of monoclonal antibodies to the CD28 surface antigen can augment the proliferation of purified human T cells stimulated with suboptimal doses of mitogens or anti...

    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.86.4.1333

    authors: Thompson CB,Lindsten T,Ledbetter JA,Kunkel SL,Young HA,Emerson SG,Leiden JM,June CH

    更新日期:1989-02-01 00:00:00

  • Synthesis of catalase in two cell-free protein-synthesizing systems and in rat liver.

    abstract::Rat liver polysomal RNA was translated in the rabbit reticulocyte lysate and in the wheat germ cell-free protein-synthesizing systems, using [(35)S]methionine as label. The catalase (hydrogen-peroxide:hydrogen-peroxide oxidoreductase, EC 1.11.1.6) that was synthesized was isolated by immunoprecipitation and characteri...

    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.75.9.4344

    authors: Robbi M,Lazarow PB

    更新日期:1978-09-01 00:00:00

  • Different mouse mast cell populations express various combinations of at least six distinct mast cell serine proteases.

    abstract::Mouse serosal mast cells (SMCs) and Kirsten sarcoma virus-immortalized mast cells store large amounts of mast cell carboxypeptidase A and serine proteases in their secretory granules. Secretory granule proteins from 2.6 x 10(6) purified SMCs were separated by NaDodSO4/PAGE, trans-blotted to poly(vinylidine difluoride)...

    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.87.8.3230

    authors: Reynolds DS,Stevens RL,Lane WS,Carr MH,Austen KF,Serafin WE

    更新日期:1990-04-01 00:00:00

  • Bmi1 lineage tracing identifies a self-renewing pancreatic acinar cell subpopulation capable of maintaining pancreatic organ homeostasis.

    abstract::A central question in stem cell biology is whether organ homeostasis is maintained in adult organs through undifferentiated stem cells or self-duplication of specialized cell populations. To address this issue in the exocrine pancreas we analyzed the Bmi1-labeled cell lineage of pancreatic acinar cells. Previously, we...

    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.0902508106

    authors: Sangiorgi E,Capecchi MR

    更新日期:2009-04-28 00:00:00

  • Sp1-dependent activation of a synthetic promoter by human immunodeficiency virus type 1 Tat protein.

    abstract::The Tat protein coded by human immunodeficiency virus (HIV) is a strong activator of viral gene expression from the long terminal repeat (LTR). It appears that Tat-mediated trans-activation of the HIV LTR is predominantly a transcriptional event. It has been reported that Tat acts at the level of both transcriptional ...

    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.88.19.8510

    authors: Kamine J,Subramanian T,Chinnadurai G

    更新日期:1991-10-01 00:00:00

  • Copper- and copper-N-heterocyclic carbene-catalyzed C-H activating carboxylation of terminal alkynes with CO2 at ambient conditions.

    abstract::The use of carbon dioxide as a renewable and environmentally friendly source of carbon in organic synthesis is a highly attractive approach, but its real world applications remain a great challenge. The major obstacles for commercialization of most current protocols are their low catalytic performances, harsh reaction...

    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.1010962107

    authors: Yu D,Zhang Y

    更新日期:2010-11-23 00:00:00

  • DNA bending induced by Cro protein binding as demonstrated by gel electrophoresis.

    abstract::We report an approach for studying protein-induced DNA bends in solution that is based on measuring the sizes of circular DNA molecules by using two-dimensional gel electrophoresis. These circular fragments are obtained by ligating short synthetic oligonucleotides containing a protein-recognition region in the presenc...

    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.88.12.5331

    authors: Lyubchenko Y,Shlyakhtenko L,Chernov B,Harrington RE

    更新日期:1991-06-15 00:00:00

  • Resolving the HONO formation mechanism in the ionosphere via ab initio molecular dynamic simulations.

    abstract::Solar emission produces copious nitrosonium ions (NO(+)) in the D layer of the ionosphere, 60 to 90 km above the Earth's surface. NO(+) is believed to transfer its charge to water clusters in that region, leading to the formation of gaseous nitrous acid (HONO) and protonated water cluster. The dynamics of this reactio...

    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.1601651113

    authors: He R,Li L,Zhong J,Zhu C,Francisco JS,Zeng XC

    更新日期:2016-04-26 00:00:00

  • Modulation of intestinal sulfur assimilation metabolism regulates iron homeostasis.

    abstract::Sulfur assimilation is an evolutionarily conserved pathway that plays an essential role in cellular and metabolic processes, including sulfation, amino acid biosynthesis, and organismal development. We report that loss of a key enzymatic component of the pathway, bisphosphate 3'-nucleotidase (Bpnt1), in mice, both 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.1715302115

    authors: Hudson BH,Hale AT,Irving RP,Li S,York JD

    更新日期:2018-03-20 00:00:00

  • Retrolinkin, a membrane protein, plays an important role in retrograde axonal transport.

    abstract::Retrograde axonal transport plays an important role in the maintenance of neuronal functions, but the mechanism is poorly defined partly because the constituents of the retrograde transport system and their interactions have yet to be elucidated. Of special interest is how dynein/dynactin motor proteins interact 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.0602222104

    authors: Liu JJ,Ding J,Wu C,Bhagavatula P,Cui B,Chu S,Mobley WC,Yang Y

    更新日期:2007-02-13 00:00:00

  • Rethinking progesterone regulation of female reproductive cyclicity.

    abstract::The progesterone receptor (PGR) is a ligand-activated transcription factor with key roles in the regulation of female fertility. Much has been learned of the actions of PGR signaling through the use of pharmacologic inhibitors and genetic manipulation, using mouse mutagenesis. Characterization of rats with a null muta...

    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.1601825113

    authors: Kubota K,Cui W,Dhakal P,Wolfe MW,Rumi MA,Vivian JL,Roby KF,Soares MJ

    更新日期:2016-04-12 00:00:00

  • Variation and constraint in Hox gene evolution.

    abstract::Despite enormous body plan variation, genes regulating embryonic development are highly conserved. Here, we probe the mechanisms that predispose ancient regulatory genes to reutilization and diversification rather than evolutionary loss. The Hox gene fushi tarazu (ftz) arose as a homeotic gene but functions as a pair-...

    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.1210847110

    authors: Heffer A,Xiang J,Pick L

    更新日期:2013-02-05 00:00:00