Abstract:
:Chromosomal translocations are a hallmark of hematopoietic malignancies. The initial molecular events or pathways that lead to translocations in hematopoietic cells are largely unknown, particularly in the stem cell-enriched population postulated to be the initial target for these events. We used in vitro differentiation of mouse embryonic stem (ES) cells combined with an I-SceI endonuclease double-strand break (DSB) repair assay to determine the relative susceptibility of isogenic hematopoietic subpopulations to DSB-induced translocations and the mechanisms that generate them. DSB-induced reciprocal translocations were frequently observed in multipotent progenitors but significantly suppressed in actively proliferating myeloid cells. Most reciprocal translocations in multipotent progenitors resulted from repair consistent with single-strand annealing followed by gap repair. Overexpression of Rad51, a protein central to DNA strand exchange and recombination, did not further increase the frequency of recovered translocations but did increase the frequency of long-tract gene conversion events associated with loss of heterozygosity and tandem duplications. These data directly demonstrate that hematopoietic multipotent progenitor cells are particularly susceptible to the formation of chromosomal rearrangements analogous to those observed in human hematopoietic malignancies. This particular subpopulation apparently represents a window of opportunity for the initiation of potentially oncogenic events following DNA damage.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Francis R,Richardson Cdoi
10.1101/gad.1522807subject
Has Abstractpub_date
2007-05-01 00:00:00pages
1064-74issue
9eissn
0890-9369issn
1549-5477pii
21/9/1064journal_volume
21pub_type
杂志文章abstract::Ribosomal protein synthesis ceases upon maturation of Xenopus oocytes. We find that this cessation results from the dissociation of ribosomal protein mRNAs from polysomes and is accompanied by the deadenylation of these transcripts. A synthetic mRNA encoding ribosomal protein L1, microinjected into stage VI oocytes, i...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.5.598
更新日期:1988-05-01 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::An RNA-based gene silencing pathway that protects bacteria and archaea from viruses and other genome invaders is hypothesized to arise from guide RNAs encoded by CRISPR loci and proteins encoded by the cas genes. CRISPR loci contain multiple short invader-derived sequences separated by short repeats. The presence of v...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1742908
更新日期:2008-12-15 00:00:00
abstract::The sigma(28) protein is a member of the bacterial sigma(70)-family of transcription factors that directs RNA polymerase to flagellar late (class 3) promoters. The sigma(28) protein is regulated in response to flagellar assembly by the anti-sigma(28) factor FlgM. FlgM inhibits sigma(28)-dependent transcription of gene...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.380406
更新日期:2006-08-15 00:00:00
abstract::All multisubunit DNA-dependent RNA polymerases (RNAP) are zinc metalloenzymes, and at least two zinc atoms are present per enzyme molecule. RNAP residues involved in zinc binding and the functional role of zinc ions in the transcription mechanism or RNAP structure are unknown. Here, we locate four cysteine residues in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.18.2439
更新日期:1999-09-15 00:00:00
abstract::The growth suppression function of the retinoblastoma protein (RB) is mediated by its interaction with a variety of cellular proteins. RB contains at least two protein-binding pockets: the large A/B pocket, which interacts with E2F and the D-type cyclins, and the C pocket, which interacts with the nuclear c-Abl tyrosi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.1.31
更新日期:1995-01-01 00:00:00
abstract::The MMTVD/myc transgenic mice spontaneously develop oligoclonal CD4+CD8+ T-cell tumors. We used provirus insertional mutagenesis in these mice to identify putative collaborators of c-myc. We found that Notch1 was mutated in a high proportion (52%) of these tumors. Proviruses were inserted upstream of the exon coding f...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.15.1930
更新日期:1996-08-01 00:00:00
abstract::The regulation of gene transcription is critical for the proper development and growth of an organism. The transcription of protein-coding genes initiates at the RNA polymerase II core promoter, which is a diverse module that can be controlled by many different elements such as the TATA box and downstream core promote...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1698108
更新日期:2008-10-15 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::FISH analysis of well-spread chromosomes reveals that homologs are paired in vegetatively growing budding yeast diploid cells, via multiple interstitial interactions, and independent of recA homologs and mating type heterozygosity. Pairing is present during G1 and G2, and in cells arrested at G1 by mating pheromone, b...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.12.1627
更新日期:1999-06-15 00:00:00
abstract::RNase MRP is a ribonucleoprotein endoribonuclease that has been shown to cleave mitochondrial primer RNA sequences from a variety of sources. Most of the RNase MRP activity is found in the nucleus where it plays a role in the processing of 5.8S rRNA. A temperature-conditional point mutation in the yeast RNA component ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.21.2617
更新日期:1994-11-01 00:00:00
abstract::The mottler of white (mw) locus has been determined to interact with alleles of the white (w) eye color locus which are a subset of the transposable element insertion mutants. The transposable elements belong to six different types, including copia, and are located at several sites within the w gene. Three X-ray-induc...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.1.73
更新日期:1989-01-01 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) is thought to be an important, possibly essential, component of the process of tumor dissemination and metastasis. About 20%-30% of Hras mutant mouse skin carcinomas induced by chemical initiation/promotion protocols have undergone EMT. Reduced exposure to TPA-induced chronic in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.210427.112
更新日期:2013-03-15 00:00:00
abstract::The transcription cofactor MAL is regulated by free actin levels and thus by actin dynamics. MAL, together with its DNA-binding partner, SRF, is required for invasive cell migration and in experimental metastasis. Although MAL/SRF has many targets, we provide genetic evidence in both Drosophila and human cellular mode...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.237743.114
更新日期:2014-05-15 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::Mesoderm induction assays in Xenopus have implicated growth factors such as activin, Vg1, Xwnt-8, and noggin as important in directing the formation of dorsal mesoderm (Spemann's organizer). Because these growth factors are structurally very different, they presumably act through distinct cell surface receptors that i...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.24.3038
更新日期:1995-12-15 00:00:00
abstract::The recombination-activating gene 1 (RAG1) and RAG2 proteins initiate V(D)J recombination, the process that assembles the B- and T-lymphocyte antigen receptor genes of jawed vertebrates. RAG1 and RAG2 are thought to have arisen from a transposable element, but the origins of this element are not understood. We show th...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.278432.116
更新日期:2016-04-15 00:00:00
abstract::Ssn6-Tup1 regulates multiple genes in yeast, providing a paradigm for corepressor functions. Tup1 interacts directly with histones H3 and H4, and mutation of these histones synergistically compromises Ssn6-Tup1-mediated repression. In vitro, Tup1 interacts preferentially with underacetylated isoforms of H3 and H4, sug...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.829100
更新日期:2000-11-01 00:00:00
abstract::Mammalian cells mostly rely on extracellular molecules to transfer signals to other cells. However, in stress conditions, more robust mechanisms might be necessary to facilitate cell-cell communications. Cellular senescence, a stress response associated with permanent exit from the cell cycle and the development of an...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.259341.115
更新日期:2015-04-15 00:00:00
abstract::The crucifer Arabidopsis thaliana has been used widely as a model organism for the study of plant development. We describe here the development of an efficient insertional mutagenesis system in Arabidopsis that permits identification of genes by their patterns of expression during development. Transposable elements of...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.14.1797
更新日期:1995-07-15 00:00:00
abstract::Codon usage bias is a universal feature of all genomes, but its in vivo biological functions in animal systems are not clear. To investigate the in vivo role of codon usage in animals, we took advantage of the sensitivity and robustness of the Drosophila circadian system. By codon-optimizing parts of Drosophila period...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.281030.116
更新日期:2016-08-01 00:00:00
abstract::To understand how chromosome shapes are determined by actions of condensins and cohesin, we devised a series of protocols in which their levels are precisely changed in Xenopus egg extracts. When the relative ratio of condensin I to II is forced to be smaller, embryonic chromosomes become shorter and thicker, being re...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2060311
更新日期:2011-07-15 00:00:00
abstract::Most eukaryotic mRNAs are translated using a cap-dependent mechanism of translation. However, approximately 10% of mammalian mRNAs initiate translation using a cap-independent mechanism that is not well understood. These mRNAs contain an internal ribosome entry site (IRES) located in the 5' untranslated region. The cr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1832209
更新日期:2009-12-01 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::Fgf-10-deficient mice (Fgf-10(-/-)) were generated to determine the role(s) of Fgf-10 in vertebrate development. Limb bud initiation was abolished in Fgf-10(-/-) mice. Strikingly, Fgf-10(-/-) fetuses continued to develop until birth, despite the complete absence of both fore- and hindlimbs. Fgf-10 is necessary for api...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.20.3156
更新日期:1998-10-15 00:00:00
abstract::Plant water homeostasis is maintained by the phytohormone abscisic acid (ABA), which triggers stomatal pore closure in response to drought stress. We identified the Arabidopsis small guanosine triphosphatase (GTPase) protein AtRac1 as a central component in the ABA-mediated stomatal closure process. ABA treatment indu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.900401
更新日期:2001-07-15 00:00:00
abstract::Hundreds of microRNAs (miRNAs) have been discovered in metazoans and plants, and understanding of their biogenesis has advanced dramatically; however, relatively little is known about the cofactors necessary for miRNA regulation of target gene expression. In Caenorhabditis elegans, the conserved miRNA let-7 and its pa...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.17153811
更新日期:2011-10-01 00:00:00
abstract::A recent study has shown that the dimeric form of the 50-kD DNA-binding subunit of the NF-kappa B transcription factor is commonly associated with two molecules of a 65-kD protein (p65) and that p65 appears to be required for inactivation of the p50 dimer by the inhibitory subunit I kappa B. Here, we provide evidence ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.11.1975
更新日期:1990-11-01 00:00:00
abstract::Amplification of 8p11-12 in human breast cancers is associated with increased proliferation and tumor grade and reduced metastasis-free patient survival. We identified Zeppo1 (zinc finger elbow-related proline domain protein 1) (FLJ14299/ZNF703) within this amplicon as a regulator of cell adhesion, migration, and prol...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1998111
更新日期:2011-03-01 00:00:00
abstract::The Ultrabithorax (Ubx) gene of Drosophila melanogaster encodes a family of UBX proteins that are thought to specify the developmental fates of segments in the posterior thorax and anterior abdomen by controlling the expression of a set of target genes. UBX proteins bind DNA in vitro, and they activate or repress diff...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.6.1044
更新日期:1990-06-01 00:00:00