Abstract:
:Telomeres protect the ends of linear chromosomes from degradation and abnormal recombination events, and in vertebrates may be important in cellular senescence and cancer. However, very little is known about the structure of human telomeres. In this report we purify telomeres and analyze their termini. We show that following replication the daughter telomeres have different terminal overhangs in normal diploid telomerase-negative human fibroblasts. Electron microscopy of those telomeres that have long overhangs yields 200 +/- 75 nucleotides of single-stranded DNA. This overhang is four times greater than the amount of telomere shortening per division found in these cells. These results are consistent with models of telomere replication in which leading-strand synthesis generates a blunt end while lagging-strand synthesis produces a long G-rich 3' overhang, and suggest that variations in lagging-strand synthesis may regulate the rate of telomere shortening in normal diploid human cells. Our results do not exclude the possibility that nuclease processing events following leading strand synthesis result in short overhangs on one end.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Wright WE,Tesmer VM,Huffman KE,Levene SD,Shay JWdoi
10.1101/gad.11.21.2801subject
Has Abstractpub_date
1997-11-01 00:00:00pages
2801-9issue
21eissn
0890-9369issn
1549-5477journal_volume
11pub_type
杂志文章abstract::Tuberous sclerosis (TSC) is an autosomal dominant disease characterized by hamartoma formation in various organs and is caused by mutations targeting either the TSC1 or TSC2 genes. TSC1 and TSC2 proteins form a functionally interdependent dimeric complex. Phosphorylation of either TSC subunit by different kinases regu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1624008
更新日期:2008-04-01 00:00:00
abstract::Although the transporter-like protein Patched (Ptc) is genetically implicated in reception of the extracellular Hedgehog (Hh) protein signal, a clear definition of the Hh receptor is complicated by the existence of additional Hh-binding proteins and, in Drosophila, by the lack of physical evidence for direct binding o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1870310
更新日期:2010-01-01 00:00:00
abstract::Expression of the gene encoding atrial natriuretic factor (ANF) during mouse cardiac embryogenesis was studied using in situ hybridization to histologic sections. ANF mRNA was first detected in a subpopulation of myocardial cells at day 8 of embryogenesis. During day 9, abundant hybridization of the ANF probe to the a...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.7.693
更新日期:1987-09-01 00:00:00
abstract::Inspired by a zebrafish mutation, two recent studies by Creanga and colleagues (pp. 1312-1325) and Tukachinsky and colleagues have shed new light on the way in which lipidated Hedgehog proteins are secreted and released from expressing cells, suggesting a model for the sequential action of the Disp and Scube2 proteins...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.207126.112
更新日期:2012-11-15 00:00:00
abstract::The yeast HO gene is transcribed transiently during G1 as cells undergo START. START-specific HO activation requires two proteins, SWI4 and SWI6, which act via a motif (CACGA4) repeated up to 10 times within the URS2 region of the HO promoter. We identified a DNA-binding activity containing SWI4 and SWI6 that recogniz...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.11.2000
更新日期:1991-11-01 00:00:00
abstract::Transabdominal (Tab), a dominant mutation in the Bithorax Complex (BX-C) of Drosophila, creates a sexually dimorphic pattern of segmental transformation that has complete penetrance and expressivity. Specific regions within the notum of the second thoracic segment (T2) are transformed into abdominal-like cuticle; thus...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.2.111
更新日期:1987-04-01 00:00:00
abstract::Genome-wide association studies (GWASs) have identified a genetic variant of moderate effect size at 6p21.1 associated with erythrocyte traits in humans. We show that this variant affects an erythroid-specific enhancer of CCND3. A Ccnd3 knockout mouse phenocopies these erythroid phenotypes, with a dramatic increase in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.197020.112
更新日期:2012-09-15 00:00:00
abstract::Post-translational modifications of histones are significant regulators of replication, transcription, and DNA repair. Particularly, newly synthesized histone H4 in H3/H4 heterodimers becomes acetylated on N-terminal lysine residues prior to its incorporation into chromatin. Previous studies have established that the ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.240531.114
更新日期:2014-06-01 00:00:00
abstract::The P family of transposable elements in Drosophila transpose by a cut-and-paste mechanism involving double-strand gap repair. We report here that a Drosophila mutagen-sensitive mutant, mus3O9, contains a mutation in IRBP (inverted repeat binding protein), the Drosophila homolog of the mammalian Ku p70 gene. We show t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.8.921
更新日期:1996-04-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.409507
更新日期:2007-04-15 00:00:00
abstract::The initial steps of double-stranded break (DSB) repair by homologous recombination mediated by the 5'-3' exonuclease/annealing protein pairs, RecE/RecT and Redalpha/Redbeta, were analyzed. Recombination was RecA-independent and required the expression of both components of an orthologous pair, even when the need for ...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-08-01 00:00:00
abstract::The bcl-6 proto-oncogene encodes a POZ/zinc finger transcriptional repressor expressed in germinal center (GC) B and T cells and required for GC formation and antibody affinity maturation. Deregulation of bcl-6 expression by chromosomal rearrangements and point mutations of the bcl-6 promoter region are implicated in ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.13.1953
更新日期:1998-07-01 00:00:00
abstract::The yeast SAS (Something About Silencing) complex and the histone variant H2A.Z have both previously been linked to an antisilencing function at the subtelomeric regions. SAS is an H4 Lys 16-specific histone acetyltransferase complex. Here we demonstrate that the H4 Lys 16 acetylation by SAS is required for efficient ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1439206
更新日期:2006-09-15 00:00:00
abstract::The yeast SAGA (Spt-Ada-Gcn5-acetyltransferase) coactivator complex exerts functions in gene expression, including activator interaction, histone acetylation, histone deubiquitination, mRNA export, chromatin recognition, and regulation of the basal transcription machinery. These diverse functions involve distinct modu...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.184705.111
更新日期:2012-03-15 00:00:00
abstract::Cap-dependent translation is mediated by eIF4F, a protein complex composed of three subunits as follows: eIF4E, which recognizes the mRNA 5' cap structure; eIF4A, an RNA-helicase; and eIF4G, a scaffolding protein that binds eIF4E, eIF4A, and the eIF4E-kinase Mnk1 simultaneously. eIF4E is hypophosphorylated and cap-dep...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.889201
更新日期:2001-08-15 00:00:00
abstract::How dividing mammalian cells overcome blocks to DNA replication by DNA damage, depleted nucleotide pools, or template-bound proteins is unclear. Here, we show that the response to blocked replication requires BRCA2, a suppressor of human breast cancer. By using two-dimensional gel electrophoresis, we demonstrate that ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.279003
更新日期:2003-12-15 00:00:00
abstract::Ferredoxin reductase (FDXR), a target of p53, modulates p53-dependent apoptosis and is necessary for steroidogenesis and biogenesis of iron-sulfur clusters. To determine the biological function of FDXR, we generated a Fdxr-deficient mouse model and found that loss of Fdxr led to embryonic lethality potentially due to ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.299388.117
更新日期:2017-06-15 00:00:00
abstract::TP53 is the most frequently mutated gene in human cancer. Many mutant p53 proteins exert oncogenic gain-of-function (GOF) properties that contribute to metastasis, but the mechanisms mediating these functions remain poorly defined in vivo. To elucidate how mutant p53 GOF drives metastasis, we developed a traceable som...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.304972.117
更新日期:2017-09-15 00:00:00
abstract::Long-range migrating progenitor cells generate hypaxial muscle, for instance the muscle of the limbs, hypoglossal cord, and diaphragm. We show here that migrating muscle progenitors express the chemokine receptor CXCR4. The corresponding ligand, SDF1, is expressed in limb and branchial arch mesenchyme; i.e., along the...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.346205
更新日期:2005-09-15 00:00:00
abstract::Previous work has shown that rRNA synthesis is strongly inhibited in yeast top1-top2 double mutants. Here, we show that inactivation of yeast topoisomerases can have paradoxical effects on transcription by RNA polymerase I. For example, transcription of ribosomal minigenes on extrachromosomal plasmids is greatly stimu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.7.1332
更新日期:1992-07-01 00:00:00
abstract::During embryonic development in vertebrates, the endoderm becomes patterned along the anteroposterior axis to produce distinct derivatives. How this regulation is controlled is not well understood. We report that the zebrafish hairy/enhancer of split [E(spl)]-related gene her5 plays a critical role in this process. At...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-07-01 00:00:00
abstract::Deregulated expression of the c-myc proto-oncogene can lead to apoptosis under certain physiological conditions. By introducing a conditionally active Myc allele into primary embryo fibroblasts null for p53, and into fibroblasts without endogenous p53 expression but ectopically expressing a temperature-sensitive p53 a...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.23.2817
更新日期:1994-12-01 00:00:00
abstract::The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs). Seven genes (smg-1-7, for suppressor with morphological effect on genitalia) that are essential for NMD were originally identified in the nematode Caenorhabditis elegans, and orthologs of these gene...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.417707
更新日期:2007-05-01 00:00:00
abstract::Male sexual development in the nematode Caenorhabditis elegans requires the genes fem-1, fem-2, and fem-3. The current model of sex determination portrays the FEM proteins as components of a novel signal transduction pathway, but the mechanisms involved in signaling through the pathway are not understood. We report th...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.18.2314
更新日期:1996-09-15 00:00:00
abstract::RUNX1/AML1 is required for the development of definitive hematopoiesis, and its activity is altered by mutations, deletions, and chromosome translocations in human acute leukemia. RUNX1 function can be regulated by post-translational modifications and protein-protein interactions. We show that RUNX1 is arginine-methyl...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1632608
更新日期:2008-03-01 00:00:00
abstract::Rosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ), the adipocyte-predominant nuclear receptor (NR). The classic model, involving binding of ligand to...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.237628.114
更新日期:2014-05-01 00:00:00
abstract::Start sites of DNA replication are marked by the origin recognition complex (ORC), which coordinates Mcm2-7 helicase loading to form the prereplicative complex (pre-RC). Although pre-RC assembly is well characterized in vitro, the process is poorly understood within the local chromatin environment surrounding replicat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.247924.114
更新日期:2015-01-15 00:00:00
abstract::Influenza virus unspliced NS1 mRNA, like retroviral pre-mRNAs, is efficiently exported from the nucleus and translated in the cytoplasm of infected cells. With human immunodeficiency virus (HIV), the transport of viral pre-mRNAs is facilitated by the viral Rev protein. We tested the possibility that the influenza viru...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.2.255
更新日期:1992-02-01 00:00:00
abstract::The ability to initiate organs throughout the lifecycle is a unique feature of plant development that is executed by groups of stem cells called meristems. The balance between stem cell proliferation and organ initiation is carefully regulated and ensures that organs can be initiated in regular geometric patterns. To ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.208501
更新日期:2001-10-15 00:00:00
abstract::Animals alter their reproductive programs to accommodate changes in nutrient availability, yet the connections between known nutrient-sensing systems and reproductive programs are underexplored, and whether there is a mechanism that senses nucleotide levels to coordinate germline proliferation is unknown. We establish...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.275107.115
更新日期:2016-02-01 00:00:00