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 mouse gastrulation. During this restricted developmental window, the embryo becomes hypersensitive to DNA damage induced by low dose irradiation (<0.5 Gy) and undergoes apoptosis without cell cycle arrest. Intriguingly, embryonic cells, including germ cell progenitors, but not extraembryonic cells, become hypersensitive to genotoxic stress and undergo Atm- and p53-dependent apoptosis. Thus, hypersensitivity to apoptosis in the early mouse embryo is a cell fate-dependent mechanism to ensure genomic integrity during a period of extreme proliferation and differentiation.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Heyer BS,MacAuley A,Behrendtsen O,Werb Zsubject
Has Abstractpub_date
2000-08-15 00:00:00pages
2072-84issue
16eissn
0890-9369issn
1549-5477journal_volume
14pub_type
杂志文章abstract::Cell fates in the optic neuroepithelium are determined by the combinational action of homeotic transcription factors. One of these is Vax2, a homeodomain protein that ventralizes the vertebrate eye field by repressing transcription of the Pax6 gene. We find that Vax2 shuttles between the nucleus and cytoplasm as a fun...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1462706
更新日期:2006-10-15 00:00:00
abstract::It is now well appreciated that the apoptosome, which governs caspase-dependent cell death, also drives nonapoptotic caspase activation to remodel cells. However, the determinants that specify whether the apoptosome acts to kill or remodel have yet to be identified. Here we report that Tango7 collaborates with the Dro...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.219287.113
更新日期:2013-08-01 00:00:00
abstract::In the absence of growth signals, cells exit the cell cycle and enter into G0 or quiescence. Alternatively, cells enter senescence in response to inappropriate growth signals such as oncogene expression. The molecular mechanisms required for cell cycle exit into quiescence or senescence are poorly understood. The DREA...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2034211
更新日期:2011-04-15 00:00:00
abstract::C-factor, the product of the csgA gene, is a cell-surface associated short-range intercellular signaling protein in Myxococcus xanthus. C-factor is required for at least four responses during starvation-induced fruiting body morphogenesis: rippling, aggregation, sporulation, and full expression of the csgA gene, all o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.6.740
更新日期:1996-03-15 00:00:00
abstract::The spectrum of tumors associated with oncogenic Ras in humans often differs from those in mice either treated with carcinogens or engineered to sporadically express oncogenic Ras, suggesting that the mechanism of Ras transformation may be different in humans. Ras stimulates primarily three main classes of effector pr...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.993902
更新日期:2002-08-15 00:00:00
abstract::The organizer region, or dorsal blastopore lip, plays a central role in the initiation of gastrulation and the formation of the body axis during Xenopus development. A similar process can also be induced in ectodermal explants by activin or by injection of activin mRNA into embryos. We have searched early embryo-speci...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.4.599
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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::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
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更新日期:2011-07-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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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::One of the first steps in neurogenesis is the diversification of cells along the dorsoventral axis. In Drosophila the central nervous system develops from three longitudinal columns of cells: ventral cells that express the vnd/nk2 homeobox gene, intermediate cells, and dorsal cells that express the msh homeobox gene. ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.22.3591
更新日期:1998-11-15 00:00:00
abstract::Activating JAK2 point mutations are implicated in the pathogenesis of myeloid and lymphoid malignancies, including high-risk B-cell acute lymphoblastic leukemia (B-ALL). In preclinical studies, treatment of JAK2 mutant leukemias with type I JAK2 inhibitors (e.g., Food and Drug Administration [FDA]-approved ruxolitinib...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.307504.117
更新日期:2018-06-01 00:00:00
abstract::Multiple congenital disorders often present complex phenotypes, but how the mutation of individual genetic factors can lead to multiple defects remains poorly understood. In the present study, we used human neuroepithelial (NE) cells and CHARGE patient-derived cells as an in vitro model system to identify the function...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.301887.117
更新日期:2018-01-15 00:00:00
abstract::Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC-β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical p...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.302679.117
更新日期:2017-08-15 00:00:00
abstract::Embryonic stem (ES) cells are pluripotent cells with the ability to self-renew indefinitely. These unique properties are controlled by genetic factors and chromatin structure. The exit from the self-renewing state is accompanied by changes in epigenetic chromatin modifications such as an induction in the silencing-ass...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1588207
更新日期:2007-10-15 00:00:00
abstract::Nucleosomes are positioned in the presence of the yeast repressor alpha 2 in minichromosomes containing the alpha 2 operator and on the promoters of a-cell-specific genes regulated by alpha 2. To investigate the possibility that alpha 2 directs nucleosome position through an interaction with a component of the core pa...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.3.411
更新日期:1992-03-01 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::The cytokine-activated Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway plays an important role in the control of a wide variety of biological processes. When misregulated, JAK/STAT signaling is associated with various human diseases, such as immune disorders and tumorigenesis. To gai...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1320705
更新日期:2005-08-15 00:00:00
abstract::It is postulated that the symmetric organization of plant lateral organs is based on two crossed axes, the abaxial-adaxial and the lateral axes. The PRESSED FLOWER (PRS) gene, the expression and function of which are dependent on the lateral axis, is reported in this study. In the prs mutant, growth of the lateral sep...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.931001
更新日期:2001-12-15 00:00:00
abstract::Chromatin structure is believed to be important for a number of cellular processes, including transcription. However, the role of nucleosomes in transcription is not well understood. We have identified the yeast histone locus HTB1-HTB1, encoding histones H2A and H2B, as a suppressor of solo delta insertion mutations t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.2.150
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abstract::Histone methylation plays an important role in regulating gene expression. One such methylation occurs at Lys 79 of histone H3 (H3K79) and is catalyzed by the yeast DOT1 (disruptor of telomeric silencing) and its mammalian homolog, DOT1L. Previous studies have demonstrated that germline disruption of Dot1L in mice res...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2018511
更新日期:2011-02-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.10.1263
更新日期:1995-05-15 00:00:00
abstract::We report a systematic mutational analysis of the helix-turn-helix motif (HTH) of the fushi tarazu (ftz) homeo domain (HD) of Drosophila. We started out by testing the function of chimeric ftz proteins containing either a part of the Sex combs reduced (Scr) or the muscle segment homeobox (msh) HDs. By complementation ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.6.1082
更新日期:1992-06-01 00:00:00
abstract::PIWI clade Argonaute proteins silence transposon expression in animal gonads. Their target specificity is defined by bound ∼23- to 30-nucleotide (nt) PIWI-interacting RNAs (piRNAs) that are processed from single-stranded precursor transcripts via two distinct pathways. Primary piRNAs are defined by the endonuclease Zu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.267252.115
更新日期:2015-08-15 00:00:00
abstract::Different RNA species are exported from the nucleus by distinct mechanisms. Among the different RNAs, mRNAs and major spliceosomal U snRNAs share several structural similarities, yet they are exported by distinct factors. We previously showed that U1 snRNAs behaved like an mRNA in nuclear export if various approximate...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1216204
更新日期:2004-09-01 00:00:00
abstract::MicroRNAs are important regulators in many cellular processes, including stem cell self-renewal. Recent studies demonstrated their function as pluripotency factors with the capacity for somatic cell reprogramming. However, their role in human embryonic stem (ES) cells (hESCs) remains poorly understood, partially due t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.17221311
更新日期:2011-10-15 00:00:00
abstract::Cdc42p, a Rho-related GTP-binding protein, regulates cytoskeletal polarization and rearrangements in eukaryotic cells, but the effectors mediating this control remain unknown. Through the use of the complete yeast genomic sequence, we have identified two novel Cdc42p targets, Gic1p and Gic2p, which contain consensus C...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.22.2972
更新日期:1997-11-15 00:00:00
abstract::The ECS (Elongin B/C-Cul2/Cul5-SOCS-box protein) complex is a member of a family of ubiquitin ligases that share a Cullin-Rbx module. SOCS-box proteins recruit substrates to the ECS complex and are linked to Cullin-Rbx via Elongin B/C. VHL has been implicated as a SOCS-box protein, but lacks a C-terminal sequence (dow...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1252404
更新日期:2004-12-15 00:00:00
abstract::Translation initiation factor 2 (eIF2) bound to GTP transfers the initiator methionyl tRNA to the 40S ribosomal subunit. The eIF5 stimulates GTP hydrolysis by the eIF2/GTP/Met-tRNA(i)(Met) ternary complex on base-pairing between Met-tRNA(i)(Met) and the start codon. The eIF2, eIF5, and eIF1 all have been implicated in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.831800
更新日期:2000-10-01 00:00:00
abstract::Mammalian histone gene transcription is increased approximately fivefold during the transition from the G1 phase to the S phase of the cell cycle. In this study, we present a detailed in vivo analysis of the human histone H2b promoter, which establishes that transcriptional regulation of this gene is mediated by a sub...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.1.32
更新日期:1988-01-01 00:00:00