Abstract:
:Faithful inheritance of genetic information requires that DNA be copied only once each cell cycle. Initiation of DNA replication involves the establishment of a prereplication complex (pre-RC) and subsequent activation by CDK/cyclins, converting the pre-RC to a post-RC. The origin recognition complex (ORC), Cdc6p, and the MCM proteins are required for establishing the pre-RC. We show that all six ORC subunits remain bound to chromatin throughout the cell cycle, whereas the MCM proteins cycle on and off, corresponding precisely to transitions of the RC. A newly isolated cdc6 mutant displays promiscuous initiation of DNA replication, increased nuclear DNA content, and constant MCM protein association with chromatin throughout the cell cycle. This gain-of-function cdc6 mutant ignores the negative controls imposed normally on initiation by the CDK/cyclins, suggesting that Cdc6p is a key mediator of once-per-cell-cycle control of DNA replication.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Liang C,Stillman Bdoi
10.1101/gad.11.24.3375subject
Has Abstractpub_date
1997-12-15 00:00:00pages
3375-86issue
24eissn
0890-9369issn
1549-5477journal_volume
11pub_type
杂志文章abstract::O(6)-Methylguanine ((Me)G) is a highly cytotoxic DNA modification generated by S(N)1-type methylating agents. Despite numerous studies implicating DNA replication, mismatch repair (MMR), and homologous recombination (HR) in (Me)G toxicity, its mode of action has remained elusive. We studied the molecular transactions ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.455407
更新日期:2007-12-15 00:00:00
abstract::Endospores of Bacillus subtilis are encased in a two-layer protein shell known as the coat, which consists of a lammellar-like inner layer and an electron-dense outer layer. We report the cloning of the structural gene (designated cotE) for an alkali-soluble coat protein of 24 kD and show that the cotE gene product is...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.8.1047
更新日期:1988-08-01 00:00:00
abstract::MicF, one of the first chromosomally encoded regulatory small RNAs (sRNAs) to be discovered, was found to modulate the expression of OmpF, an abundant outer membrane protein. Several recent papers have now shown that this is not an isolated case. At least five other sRNAs also regulate the synthesis of outer membrane ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1457506
更新日期:2006-09-01 00:00:00
abstract::DNA loops that juxtapose the promoter and terminator regions of RNA polymerase II-transcribed genes have been identified in yeast and mammalian cells. Loop formation is transcription-dependent and requires components of the pre-mRNA 3'-end processing machinery. Here we report that looping at the yeast GAL10 gene persi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1823609
更新日期:2009-11-15 00:00:00
abstract::We investigated the regulation of the activin/nodal-inducible distal element (DE) of the Xenopus goosecoid (gsc) promoter. On the basis of its interaction with the DE, we isolated a Xenopus homolog of the human Williams-Beuren syndrome critical region 11 (XWBSCR11), and further, show that it interacts with pathway-spe...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.963802
更新日期:2002-04-01 00:00:00
abstract::The Drosophila external sensory organ forms in a lineage elaborating from a single precursor cell via a stereotypical series of asymmetric divisions. HAMLET transcription factor expression demarcates the lineage branch that generates two internal cell types, the external sensory neuron and thecogen. In HAMLET mutant o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1170904
更新日期:2004-03-15 00:00:00
abstract::Irradiation in the G1 phase of the cell cycle delays the onset of DNA synthesis and transiently inhibits the activation of replication origins in mammalian cells. It has been suggested that this inhibition is the result of the loss of torsional tension in the DNA after it has been damaged. Because irradiation causes D...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.5.554
更新日期:1994-03-01 00:00:00
abstract::Unrepaired DNA lesions in the template strand block the replication fork. In yeast, Mec1 protein kinase-mediated replication checkpoint prevents the breakdown of replication forks and maintains viability in DNA-damaged cells going through the S phase. By ensuring that the replisome does not dissociate from the fork st...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1793409
更新日期:2009-06-15 00:00:00
abstract::Gene duplication and divergence is a major driver in the emergence of evolutionary novelties. How variations in amino acid sequences lead to loss of ancestral activity and functional diversification of proteins is poorly understood. We used cross-species functional analysis of Drosophila Labial and its mouse HOX1 orth...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.342329.120
更新日期:2020-12-01 00:00:00
abstract::Over a period of many months, Xenopus oocytes stockpile large quantities of tRNA for use during the first few hours of embryogenesis. To test the idea that these tRNAs are transcribed from one set of genes and that another set is used by somatic cells, we used synthetic oligonucleotides to analyze the sequence and ste...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.8.1190
更新日期:1989-08-01 00:00:00
abstract::Sequence-specific DNA-binding activators, key regulators of gene expression, stimulate transcription in part by targeting the core promoter recognition TFIID complex and aiding in its recruitment to promoter DNA. Although it has been established that activators can interact with multiple components of TFIID, it is unk...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1790709
更新日期:2009-07-01 00:00:00
abstract::Sex determination is regulated by diverse pathways. Although upstream signals vary, a cysteine-rich DNA-binding domain (the DM motif) is conserved within downstream transcription factors of Drosophila melanogaster (Doublesex) and Caenorhabditis elegans (MAB-3). Vertebrate DM genes have likewise been identified and, re...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-07-15 00:00:00
abstract::The current model for endocrine cell specification in the pancreas invokes high-level production of the transcription factor Neurogenin 3 (Neurog3) in Sox9(+) bipotent epithelial cells as the trigger for endocrine commitment, cell cycle exit, and rapid delamination toward proto-islet clusters. This model posits a tran...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.284729.116
更新日期:2016-08-15 00:00:00
abstract::Chromosome segregation requires stable bipolar attachments of spindle microtubules to kinetochores. The dynein/dynactin motor complex localizes transiently to kinetochores and is implicated in chromosome segregation, but its role remains poorly understood. Here, we use the Caenorhabditis elegans embryo to investigate ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1687508
更新日期:2008-09-01 00:00:00
abstract::The yeast Ste20 protein kinase is involved in pheromone response. Mammalian homologs of Ste20 exist, but their function remains unknown. We identified a novel yeast STE20 homolog, CLA4, in a screen for mutations lethal in the absence of the G1 cyclins Cln1 and Cln2. Cla4 is involved in budding and cytokinesis and inte...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.15.1817
更新日期:1995-08-01 00:00:00
abstract::Pax3 is a key transcription factor implicated in development and human disease. To dissect the role of Pax3 in myogenesis and establish whether it is a repressor or activator, we generated loss- and gain-of-function alleles by targeting an nLacZ reporter and a sequence encoding the oncogenic fusion protein PAX3-FKHR i...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.281203
更新日期:2003-12-01 00:00:00
abstract::Nitric oxide (NO) is an important second messenger involved in numerous biological processes, but how it regulates gene expression is not well understood. In this issue of Genes & Development, Cáceres and colleagues (pp. 1476-1485) report a critical requirement of NO as a direct regulator of gene expression through it...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.2080411
更新日期:2011-07-15 00:00:00
abstract::Gastrulation in mice is associated with the start of extreme proliferation and differentiation. The potential cost to the embryo of a very rapid proliferation rate is a high production of damaged cells. We demonstrate a novel surveillance mechanism for the elimination of cells damaged by ionizing radiation during mous...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-08-15 00:00:00
abstract::The Brr2 helicase provides the key remodeling activity for spliceosome catalytic activation, during which it disrupts the U4/U6 di-snRNP (small nuclear RNA protein), and its activity has to be tightly regulated. Brr2 exhibits an unusual architecture, including an ∼ 500-residue N-terminal region, whose functions and mo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.271528.115
更新日期:2015-12-15 00:00:00
abstract::Specific recognition of splice sites within metazoan mRNA precursors (pre-mRNAs) is a potential stage for gene regulation by alternative splicing. Splicing factors of the SR protein family play a major role in this regulation, as they are required for early recognition of splice sites during spliceosome assembly. Here...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.6.740
更新日期:1999-03-15 00:00:00
abstract::The Snail zinc-finger transcription factors trigger epithelial-mesenchymal transitions (EMTs), endowing epithelial cells with migratory and invasive properties during both embryonic development and tumor progression. During EMT, Snail provokes the loss of epithelial markers, as well as changes in cell shape and the ex...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.294104
更新日期:2004-05-15 00:00:00
abstract::Somitogenesis involves the segmentation of the paraxial mesoderm into units along the anteroposterior axis. Here we show a role for Eph and ephrin signaling in the patterning of presomitic mesoderm and formation of the somites. Ephrin-A-L1 and ephrin-B2 are expressed in an iterative manner in the developing somites an...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.19.3096
更新日期:1998-10-01 00:00:00
abstract::By studying neuroectoderm formation in the absence of mesoderm and mesectoderm in mutants of the zygotic genes snail and twist, we have found that the number of neuroblasts is not reduced in these mutants, suggesting that mesoderm and mesectoderm are not essential for the initiation of neural development. The position...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.9.1577
更新日期:1991-09-01 00:00:00
abstract::Post-translational modifications of conserved N-terminal tail residues in histones regulate many aspects of chromosome activity. Thr 3 of histone H3 is highly conserved, but the significance of its phosphorylation is unclear, and the identity of the corresponding kinase unknown. Immunostaining with phospho-specific an...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1267105
更新日期:2005-02-15 00:00:00
abstract::Alternative splicing factor/splicing factor 2 (ASF/SF2) is the prototype of a family of nuclear proteins highly conserved throughout metazoa, the SR (serine/arginine) proteins. Based largely on in vitro studies, SR proteins have been suggested to play important roles in constitutive and alternative splicing of pre-mRN...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.20.2588
更新日期:1996-10-15 00:00:00
abstract::The widespread class of RNA viruses that utilize internal ribosome entry sites (IRESs) for translation include poliovirus and Hepatitis C virus. To identify host factors required for IRES-dependent translation and viral replication, we performed a genome-wide RNAi screen in Drosophila cells infected with Drosophila C ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1267905
更新日期:2005-02-15 00:00:00
abstract::DNA replication remains unfinished in many Drosophila polyploid cells, which harbor disproportionately fewer copies of late-replicating chromosomal regions. By analyzing paired-end high-throughput sequence data from polytene larval salivary gland cells, we define 112 underreplicated (UR) euchromatic regions 60-480 kb ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.245811.114
更新日期:2014-08-15 00:00:00
abstract::We hypothesized that basic helix-loop-helix (bHLH) MIST1 (BHLHA15) is a "scaling factor" that universally establishes secretory morphology in cells that perform regulated secretion. Here, we show that targeted deletion of MIST1 caused dismantling of the secretory apparatus of diverse exocrine cells. Parietal cells (PC...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.285684.116
更新日期:2017-01-15 00:00:00
abstract::Homeotic genes are expressed in spatially precise patterns during Drosophila development to control segmental differentiation. The Sex combs reduced (Scr) gene of the Antennapedia gene complex is involved in the determination of the labial and prothoracic segments of the embryo. To study both the wild-type pattern of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.7.716
更新日期:1987-09-01 00:00:00
abstract::The Notch signaling pathway is essential for embryonic vascular development in vertebrates. Here we show that mouse embryos heterozygous for a targeted mutation in the gene encoding the DLL4 ligand exhibit haploinsufficient lethality because of defects in vascular remodeling. We also describe vascular defects in embry...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1239204
更新日期:2004-10-15 00:00:00