DNA polymerases and somatic hypermutation of immunoglobulin genes.


:Somatic hypermutation of immunoglobulin variable genes, which increases antibody diversity, is initiated by the activation-induced cytosine deaminase (AID) protein. The current DNA-deamination model posits that AID deaminates cytosine to uracil in DNA, and that mutations are generated by DNA polymerases during replication or repair of the uracil residue. Mutations could arise as follows: by DNA replicating past the uracil; by removing the uracil with a uracil glycosylase and replicating past the resulting abasic site with a low-fidelity polymerase; or by repairing the uracil and synthesizing a DNA-repair patch downstream using a low-fidelity polymerase. In this review, we summarize the biochemical properties of specialized DNA polymerases in mammalian cells and discuss their participation in the mechanisms of hypermutation. Many recent studies have examined mice deficient in the genes that encode various DNA polymerases, and have shown that DNA polymerase H (POLH) contributes to hypermutation, whereas POLI, POLK and several other enzymes do not have major roles. The low-fidelity enzyme POLQ has been proposed as another candidate polymerase because it can efficiently bypass abasic sites and recent evidence indicates that it might participate in hypermutation.




EMBO reports


Seki M,Gearhart PJ,Wood RD





Has Abstract


2005-12-01 00:00:00














  • R3hdml regulates satellite cell proliferation and differentiation.

    abstract::In this study, we identified a previously uncharacterized skeletal satellite cell-secreted protein, R3h domain containing-like (R3hdml). Expression of R3hdml increases during skeletal muscle development and differentiation in mice. Body weight and skeletal muscle mass of R3hdml knockout (KO) mice are lower compared to...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Sakamoto K,Furuichi Y,Yamamoto M,Takahashi M,Akimoto Y,Ishikawa T,Shimizu T,Fujimoto M,Takada-Watanabe A,Hayashi A,Mita Y,Manabe Y,Fujii NL,Ishibashi R,Maezawa Y,Betsholtz C,Yokote K,Takemoto M

    更新日期:2019-11-05 00:00:00

  • PIDDosome-induced p53-dependent ploidy restriction facilitates hepatocarcinogenesis.

    abstract::Polyploidization frequently precedes tumorigenesis but also occurs during normal development in several tissues. Hepatocyte ploidy is controlled by the PIDDosome during development and regeneration. This multi-protein complex is activated by supernumerary centrosomes to induce p53 and restrict proliferation of polyplo...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Sladky VC,Knapp K,Szabo TG,Braun VZ,Bongiovanni L,van den Bos H,Spierings DC,Westendorp B,Curinha A,Stojakovic T,Scharnagl H,Timelthaler G,Tsuchia K,Pinter M,Semmler G,Foijer F,de Bruin A,Reiberger T,Rohr-Udilova N,

    更新日期:2020-11-23 00:00:00

  • Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1.

    abstract::RNA binding proteins, including IMP1/IGF2BP1, are essential regulators of intestinal development and cancer. Imp1 hypomorphic mice exhibit gastrointestinal growth defects, yet the specific role for IMP1 in colon epithelial repair is unclear. Our prior work revealed that intestinal epithelial cell-specific Imp1 deletio...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Chatterji P,Williams PA,Whelan KA,Samper FC,Andres SF,Simon LA,Parham LR,Mizuno R,Lundsmith ET,Lee DS,Liang S,Wijeratne HS,Marti S,Chau L,Giroux V,Wilkins BJ,Wu GD,Shah P,Tartaglia GG,Hamilton KE

    更新日期:2019-06-01 00:00:00

  • Effects of reciprocal chromosomal translocations on the fitness of Saccharomyces cerevisiae.

    abstract::Yeast species have undergone extensive genome reorganization in their evolutionary history, including variations in chromosome number and large chromosomal rearrangements, such as translocations. To determine directly the contribution of chromosomal translocations to the whole organism's fitness, we devised a strategy...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Colson I,Delneri D,Oliver SG

    更新日期:2004-04-01 00:00:00

  • The intramembrane protease SPPL2c promotes male germ cell development by cleaving phospholamban.

    abstract::Signal peptide peptidase (SPP) and the four homologous SPP-like (SPPL) proteases constitute a family of intramembrane aspartyl proteases with selectivity for type II-oriented transmembrane segments. Here, we analyse the physiological function of the orphan protease SPPL2c, previously considered to represent a non-expr...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Niemeyer J,Mentrup T,Heidasch R,Müller SA,Biswas U,Meyer R,Papadopoulou AA,Dederer V,Haug-Kröper M,Adamski V,Lüllmann-Rauch R,Bergmann M,Mayerhofer A,Saftig P,Wennemuth G,Jessberger R,Fluhrer R,Lichtenthaler SF,Lember

    更新日期:2019-03-01 00:00:00

  • Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest.

    abstract::Individuals affected by the autosomal recessive disorder Werner's syndrome (WS) develop many of the symptoms characteristic of premature ageing. Primary fibroblasts cultured from WS patients exhibit karyotypic abnormalities and a reduced replicative life span. The WRN gene encodes a 3'-5' DNA helicase, and is a member...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Constantinou A,Tarsounas M,Karow JK,Brosh RM,Bohr VA,Hickson ID,West SC

    更新日期:2000-07-01 00:00:00

  • Retinoblastoma protein promotes uterine epithelial cell cycle arrest and necroptosis for embryo invasion.

    abstract::Retinoblastoma protein (RB) encoded by Rb1 is a prominent inducer of cell cycle arrest (CCA). The hormone progesterone (P4 ) promotes CCA in the uterine epithelium and previous studies indicated that P4 activates RB by reducing the phosphorylated, inactive form of RB. Here, we show that embryo implantation is impaired...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Akaeda S,Hirota Y,Fukui Y,Aikawa S,Shimizu-Hirota R,Kaku T,Gebril M,Hirata T,Hiraoka T,Matsuo M,Haraguchi H,Saito-Kanatani M,Takeda N,Fujii T,Osuga Y

    更新日期:2021-01-05 00:00:00

  • Structural basis for receptor recognition and pore formation of a zebrafish aerolysin-like protein.

    abstract::Various aerolysin-like pore-forming proteins have been identified from bacteria to vertebrates. However, the mechanism of receptor recognition and/or pore formation of the eukaryotic members remains unknown. Here, we present the first crystal and electron microscopy structures of a vertebrate aerolysin-like protein fr...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Jia N,Liu N,Cheng W,Jiang YL,Sun H,Chen LL,Peng J,Zhang Y,Ding YH,Zhang ZH,Wang X,Cai G,Wang J,Dong MQ,Zhang Z,Wu H,Wang HW,Chen Y,Zhou CZ

    更新日期:2016-02-01 00:00:00

  • The FKBP12-rapamycin-associated protein (FRAP) is a CLIP-170 kinase.

    abstract::CLIP-170/Restin belongs to a family of conserved microtubule (MT)-associated proteins, which are important for MT organization and functions. CLIP-170 is a phosphoprotein and phosphorylation is thought to regulate the binding of CLIP-170 to MTs. However, little is known about the kinase(s) involved. In this study, we ...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Choi JH,Bertram PG,Drenan R,Carvalho J,Zhou HH,Zheng XF

    更新日期:2002-10-01 00:00:00

  • The 18S rRNA m6 A methyltransferase METTL5 promotes mouse embryonic stem cell differentiation.

    abstract::RNA modifications represent a novel layer of regulation of gene expression. Functional experiments revealed that N6 -methyladenosine (m6 A) on messenger RNA (mRNA) plays critical roles in cell fate determination and development. m6 A mark also resides in the decoding center of 18S ribosomal RNA (rRNA); however, the bi...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Xing M,Liu Q,Mao C,Zeng H,Zhang X,Zhao S,Chen L,Liu M,Shen B,Guo X,Ma H,Chen H,Zhang J

    更新日期:2020-10-05 00:00:00

  • Oncogenic KRAS signaling activates mTORC1 through COUP-TFII-mediated lactate production.

    abstract::Oncogenic signals contribute to enhanced glycolysis and mTORC1 activity, leading to rapid cell proliferation in cancer. Regulation of glycolysis and mTORC1 by PI3K/Akt signaling is well established, but how KRAS-induced MEK signaling regulates these pathways remains poorly understood. Here, we report a role for MEK-dr...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Byun JK,Park M,Yun JW,Lee J,Kim JS,Cho SJ,Lee YM,Lee IK,Choi YK,Park KG

    更新日期:2019-06-01 00:00:00

  • Portugal's prominence in malaria research: How a small country became a key player in European research on one of the world's deadliest diseases.

    abstract::Despite its limited resources, Portugal has gained a prominent position in research on malaria. Several historical and personal factors have contributed to this achievement. ...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Prudêncio M

    更新日期:2021-01-10 00:00:00

  • Alternative editing of cytochrome c oxidase III mRNA in trypanosome mitochondria generates protein diversity.

    abstract::Trypanosomes use RNA editing to produce most functional mitochondrial messenger RNA. Precise insertion and deletion of hundreds of uridines is necessary to make full-length cytochrome c oxidase III (COXIII) mRNA. We show that COXIII mRNA can be alternatively edited by a mechanism using an alternative guide RNA to make...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Ochsenreiter T,Hajduk SL

    更新日期:2006-11-01 00:00:00

  • Hrs mediates downregulation of multiple signalling receptors in Drosophila.

    abstract::Endocytosis and subsequent lysosomal degradation of activated signalling receptors can attenuate signalling. Endocytosis may also promote signalling by targeting receptors to specific compartments. A key step regulating the degradation of receptors is their ubiquitination. Hrs/Vps27p, an endosome-associated, ubiquitin...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Jékely G,Rørth P

    更新日期:2003-12-01 00:00:00

  • Initiation of epigenetic reprogramming of the X chromosome in somatic nuclei transplanted to a mouse oocyte.

    abstract::The active and inactive X chromosomes have distinct epigenetic marks in somatic nuclei, which undergo reprogramming after transplantation into oocytes. We show that, despite the disappearance of Xist RNA coating in 30 min, the epigenetic memory of the inactive X persists with the precocious appearance of histone H3 tr...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Bao S,Miyoshi N,Okamoto I,Jenuwein T,Heard E,Azim Surani M

    更新日期:2005-08-01 00:00:00

  • The FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activity.

    abstract::Hypoxic and oxidant stresses can coexist in biological systems, and oxidant stress has been proposed to activate hypoxia pathways through the inactivation of the 'oxygen-sensing' hypoxia-inducible factor (HIF) prolyl and asparaginyl hydroxylases. Here, we show that despite reduced sensitivity to cellular hypoxia, the ...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Masson N,Singleton RS,Sekirnik R,Trudgian DC,Ambrose LJ,Miranda MX,Tian YM,Kessler BM,Schofield CJ,Ratcliffe PJ

    更新日期:2012-03-01 00:00:00

  • ADAR1 promotes robust hypoxia signaling via distinct regulation of multiple HIF-1α-inhibiting factors.

    abstract::Adenosine deaminase acting on RNA (ADAR)-catalyzed adenosine-to-inosine RNA editing is potentially dysregulated in neoplastic progression. However, how this transcriptome recoding process is functionally correlated with tumorigenesis remains largely elusive. Our analyses of RNA editome datasets identify hypoxia-relate...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Ma CP,Liu H,Yi-Feng Chang I,Wang WC,Chen YT,Wu SM,Chen HW,Kuo YP,Shih CT,Li CY,Tan BC

    更新日期:2019-05-01 00:00:00

  • Glutamyl-tRNA mediates a switch in RNA polymerase use during chloroplast biogenesis.

    abstract::Chloroplast genes of higher plants are transcribed by two types of RNA polymerase that are encoded by nuclear (NEP (nuclear-encoded plastid RNA polymerase)) or plastid (PEP (plastid-encoded plastid RNA polymerase)) genomes. NEP is largely responsible for the transcription of housekeeping genes during early chloroplast...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Hanaoka M,Kanamaru K,Fujiwara M,Takahashi H,Tanaka K

    更新日期:2005-06-01 00:00:00

  • An extracellular microRNA can rescue lives in sepsis.

    abstract::Sepsis, or blood poisoning, is a savage response of the body to infection. It can lead to organ failure, blood pressure decline, heart failure, and coma. Between 20 and 30 million people suffer from sepsis each year, leading to 8 million deaths. Although certain people are more at risk than others (young children, eld...

    journal_title:EMBO reports

    pub_type: 评论,新闻


    authors: Van Looveren K,Van Wyngene L,Libert C

    更新日期:2020-01-07 00:00:00

  • Effect of CpG methylation on RAG1/RAG2 reactivity: implications of direct and indirect mechanisms for controlling V(D)J cleavage.

    abstract::It has been suggested that DNA methylation/demethylation is involved in regulating V(D)J rearrangement. Although methylated DNA is thought to induce an inaccessible chromatin structure, it is unclear whether DNA methylation can directly control V(D)J recombination independently of chromatin structure. In this study, w...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Nakase H,Takahama Y,Akamatsu Y

    更新日期:2003-08-01 00:00:00

  • Structure of the ubiquitin-binding zinc finger domain of human DNA Y-polymerase eta.

    abstract::The ubiquitin-binding zinc finger (UBZ) domain of human DNA Y-family polymerase (pol) eta is important in the recruitment of the polymerase to the stalled replication machinery in translesion synthesis. Here, we report the solution structure of the pol eta UBZ domain and its interaction with ubiquitin. We show that th...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Bomar MG,Pai MT,Tzeng SR,Li SS,Zhou P

    更新日期:2007-03-01 00:00:00

  • Ars Moriendi; the art of dying well - new insights into the molecular pathways of necroptotic cell death.

    abstract::When our time comes to die most people would probably opt for a quick, peaceful and painless exit. But the manner and timing are rarely under our direct control. Hence the Ars moriendi, literally, "The Art of Dying", two texts written in Latin around the 15th century that offered advice on how to die well according to...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审


    authors: Murphy JM,Silke J

    更新日期:2014-02-01 00:00:00

  • Understanding human genetic variation in the era of high-throughput sequencing.

    abstract::The EMBO/EMBL symposium 'Human Variation: Cause and Consequence' highlighted advances in understanding the molecular basis of human genetic variation and its myriad implications for biology, human origins and disease. As high-throughput sequencing allows us to define genetic variation and its functional consequences a...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Knight JC

    更新日期:2010-09-01 00:00:00

  • Dynamic survey of mitochondria by ubiquitin.

    abstract::Ubiquitin is a post-translational modifier with proteolytic and non-proteolytic roles in many biological processes. At mitochondria, it performs regulatory homeostatic functions and contributes to mitochondrial quality control. Ubiquitin is essential for mitochondrial fusion, regulates mitochondria-ER contacts, and pa...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审


    authors: Escobar-Henriques M,Langer T

    更新日期:2014-03-01 00:00:00

  • c-di-AMP reports DNA integrity during sporulation in Bacillus subtilis.

    abstract::The bacterium Bacillus subtilis produces the DNA integrity scanning protein (DisA), a checkpoint protein that delays sporulation in response to DNA damage. DisA scans the chromosome and pauses at sites of DNA lesions. Structural analysis showed that DisA synthesizes the small molecule cyclic diadenosine monophosphate ...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Oppenheimer-Shaanan Y,Wexselblatt E,Katzhendler J,Yavin E,Ben-Yehuda S

    更新日期:2011-06-01 00:00:00

  • The [URE3] phenotype: evidence for a soluble prion in yeast.

    abstract::The aggregation of the two yeast proteins Sup35p and Ure2p is widely accepted as a model for explaining the prion propagation of the phenotypes [PSI+] and [URE3], respectively. Here, we demonstrate that the propagation of [URE3] cannot simply be the consequence of generating large aggregates of Ure2p, because such agg...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Fernandez-Bellot E,Guillemet E,Ness F,Baudin-Baillieu A,Ripaud L,Tuite M,Cullin C

    更新日期:2002-01-01 00:00:00

  • Institutional ELN/LIMS deployment: Highly customizable ELN/LIMS platform as a cornerstone of digital transformation for life sciences research institutes.

    abstract::The systematic recording and management of experimental data in academic life science research remains an open problem. EPFL engaged in a program of ELN/LIMS deployment 6 years ago, encountering a host of fundamental questions at the institutional level and in each single laboratory. Here, based on our experience we a...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Argento N

    更新日期:2020-03-04 00:00:00

  • Yarrowia lipolytica Pex20p, Saccharomyces cerevisiae Pex18p/Pex21p and mammalian Pex5pL fulfil a common function in the early steps of the peroxisomal PTS2 import pathway.

    abstract::Import of peroxisomal matrix proteins is essential for peroxisome biogenesis. Genetic and biochemical studies using a variety of different model systems have led to the discovery of 23 PEX genes required for this process. Although it is generally believed that, in contrast to mitochondria and chloroplasts, translocati...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Einwächter H,Sowinski S,Kunau WH,Schliebs W

    更新日期:2001-11-01 00:00:00

  • The dynamic organization of gene-regulatory machinery in nuclear microenvironments.

    abstract::Nuclear components are functionally linked with the dynamic temporal and spatial compartmentalization, sorting and integration of regulatory information to facilitate its selective use. For example, the subnuclear targeting of transcription factors to punctate sites in the interphase nucleus mechanistically couples ch...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审


    authors: Zaidi SK,Young DW,Choi JY,Pratap J,Javed A,Montecino M,Stein JL,van Wijnen AJ,Lian JB,Stein GS

    更新日期:2005-02-01 00:00:00

  • Visualization of cytosolic ribosomes on the surface of mitochondria by electron cryo-tomography.

    abstract::We employed electron cryo-tomography to visualize cytosolic ribosomes on the surface of mitochondria. Translation-arrested ribosomes reveal the clustered organization of the TOM complex, corroborating earlier reports of localized translation. Ribosomes are shown to interact specifically with the TOM complex, and nasce...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Gold VA,Chroscicki P,Bragoszewski P,Chacinska A

    更新日期:2017-10-01 00:00:00