Abstract:
:Cell cycle checkpoints are critical for genomic stability. Rad17, a component of the checkpoint clamp loader complex (Rad17/Rfc2-5), is required for the response to DNA damage and replication stress. To explore the role of Rad17 in the maintenance of genomic integrity, we established somatic conditional alleles of RAD17 in human cells. We find that RAD17 is not only important for the Atr-mediated checkpoint but is also essential for cell viability. Cells lacking RAD17 exhibited acute chromosomal aberrations and underwent endoreduplication at a high rate. Therefore, RAD17 links the checkpoint to ploidy control and is essential for the maintenance of chromosomal stability.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Wang X,Zou L,Zheng H,Wei Q,Elledge SJ,Li Ldoi
10.1101/gad.1065103subject
Has Abstractpub_date
2003-04-15 00:00:00pages
965-70issue
8eissn
0890-9369issn
1549-5477pii
U-10651Rspjournal_volume
17pub_type
杂志文章abstract::A novel 15-kDa protein, RbfA, has been identified by virtue of its ability to act as a high copy suppressor of a previously characterized dominant cold-sensitive mutation (C23U) in 16S rRNA. RbfA is found associated with free 30S ribosomal subunits, but not with 70S ribosomes or polysomes, and is essential for maximal...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.5.626
更新日期:1995-03-01 00:00:00
abstract::Kinase suppressor of Ras (KSR) is a recently identified component of Ras-dependent signaling pathways. In this report, we show that murine KSR1 (mKSR1) cooperates with activated Ras to promote Xenopus oocyte maturation and cellular transformation and provide evidence that this cooperation occurs by accelerating mitoge...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.21.2684
更新日期:1996-11-01 00:00:00
abstract::Bloom's syndrome (BS) is an autosomal recessive disorder characterized by a strong cancer predisposition. The defining feature of BS is extreme genome instability. The gene mutated in Bloom's syndrome, BLM, encodes a DNA helicase (BLM) of the RecQ family. BLM plays a role in homologous recombination; however, its exac...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1609007
更新日期:2007-12-01 00:00:00
abstract::The cJun N-terminal kinase 1 (JNK1) is implicated in diet-induced obesity. Indeed, germline ablation of the murine Jnk1 gene prevents diet-induced obesity. Here we demonstrate that selective deficiency of JNK1 in the murine nervous system is sufficient to suppress diet-induced obesity. The failure to increase body mas...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1878510
更新日期:2010-02-01 00:00:00
abstract::The neurogenic loci of Drosophila are required for proper partitioning of ectodermal cells into epidermal versus neural lineages. The loci appear to encode components of a developmental pathway involving cellular communication. In an effort to understand the role of the neurogenic locus mastermind in these processes, ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.10.1688
更新日期:1990-10-01 00:00:00
abstract::The assembly of a nervous system requires the extension of axons and dendrites to specific regions where they are matched with appropriate synaptic targets. Although the cues that guide long-range outgrowth have been characterized extensively, additional mechanisms are required to explain short-range guidance in neura...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.259838.115
更新日期:2015-05-15 00:00:00
abstract::We report the discovery of mRNA 5'-leader trans-splicing (SL trans-splicing) in the chordates. In the ascidian protochordate Ciona intestinalis, the mRNAs of at least seven genes undergo trans-splicing of a 16-nucleotide 5'-leader apparently derived from a 46-nucleotide RNA that shares features with previously charact...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.865401
更新日期:2001-02-01 00:00:00
abstract::Fibro-adipogenic progenitors (FAPs) reside in the muscle, where they facilitate myofiber regeneration. Under normal conditions, FAPs lack myogenic potential and thus do not directly contribute to regenerated myofibers. Surprisingly, Saccone and colleagues (pp. 841-857) demonstrated that the dystrophic muscle environme...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.241182.114
更新日期:2014-04-15 00:00:00
abstract::Pseudoplasmodia of developing Dictyostelium are organized with anteroposterior polarity. We have isolated CAR4, the gene for a new cell-surface, G protein-linked cAMP receptor. CAR4 mRNA is initially expressed during tip elongation and continues to accumulate into culmination. CAR4 is maximally expressed in pseudoplas...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.17.2086
更新日期:1994-09-01 00:00:00
abstract::Nuclear export factor 1 (NXF1) exports mRNA to the cytoplasm after recruitment to mRNA by specific adaptor proteins. How and why cells use numerous different export adaptors is poorly understood. Here we critically evaluate members of the SR protein family (SRSF1-7) for their potential to act as NXF1 adaptors that cou...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.276477.115
更新日期:2016-03-01 00:00:00
abstract::The human Y-family DNA polymerases, Poliota, Poleta, and Polkappa, function in promoting replication through DNA lesions. However, because of their low fidelity, any involvement of these polymerases in DNA synthesis during base excision repair (BER) would be highly mutagenic. Mechanisms, therefore, must exist to exclu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1146103
更新日期:2003-11-15 00:00:00
abstract::Telomeres are specialized nucleoprotein structures that protect chromosome ends from DNA damage response (DDR) and DNA rearrangements. The telomeric shelterin protein TRF2 suppresses the DDR, and this function has been attributed to its abilities to trigger t-loop formation or prevent massive decompaction and loss of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.294082.116
更新日期:2017-03-15 00:00:00
abstract::Inactivation of cyclin B-Cdc2 kinase at the exit from M phase depends on the specific proteolysis of the cyclin B subunit, whereas the Cdc2 subunit remains present at nearly constant levels throughout the cell cycle. It is unknown how Cdc2 escapes degradation when cyclin B is destroyed. In Xenopus egg extracts that re...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.823200
更新日期:2000-09-15 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::The serine/threonine kinase Akt/PKB is a major downstream effector of growth factor-mediated cell survival. Activated Akt, like Bcl-2 and Bcl-xL, prevents closure of a PT pore component, the voltage-dependent anion channel (VDAC); intracellular acidification; mitochondrial hyperpolarization; and the decline in oxidati...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.889901
更新日期:2001-06-01 00:00:00
abstract::The integration of viral DNA into the host genome is an essential step in the retrovirus life cycle. To understand this process better, we have examined the native state of viral DNA in cells acutely infected by murine leukemia virus (MLV), using both a physical assay for viral DNA and a functional assay for integrati...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.4.469
更新日期:1989-04-01 00:00:00
abstract::Mammalian cells possess two amino acid-sensing kinases: general control nonderepressible 2 (GCN2) and mechanistic target of rapamycin complex 1 (mTORC1). Their combined effects orchestrate cellular adaptation to amino acid levels, but how their activities are coordinated remains poorly understood. Here, we demonstrate...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.269324.115
更新日期:2015-11-15 00:00:00
abstract::The RNA polymerase II (RNAPII) C-terminal domain kinase, CDK12, regulates genome stability, expression of DNA repair genes, and cancer cell resistance to chemotherapy and immunotherapy. In addition to its role in mRNA biosynthesis of DNA repair genes, we show here that CDK12 phosphorylates the mRNA 5' cap-binding repr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.322339.118
更新日期:2019-04-01 00:00:00
abstract::Export to the cytoplasm of U3 RNA transcribed from a rat U3 gene injected into the nucleus of Xenopus oocytes indicates that the biogenesis of U3 RNA, like that of the previously studied Sm-precipitable nucleoplasmic snRNAs (U1, U2, U4, and U5), includes a cytoplasmic phase. The regulation of import of the U3 snRNA in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.6.1120
更新日期:1992-06-01 00:00:00
abstract::Plectin, a major linker and scaffolding protein of the cytoskeleton, has been shown to be essential for the mechanical integrity of skin, skeletal muscle, and heart. Studying fibroblast and astroglial cell cultures derived from plectin (-/-) mice, we found that their actin cytoskeleton, including focal adhesion contac...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.21.3442
更新日期:1998-11-01 00:00:00
abstract::Changes in the pattern of gene expression play an important role in allowing cancer cells to acquire their hallmark characteristics, while genomic instability enables cells to acquire genetic alterations that promote oncogenesis. Chromatin plays central roles in both transcriptional regulation and the maintenance of g...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.255182.114
更新日期:2015-02-01 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::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::Bone metastases are the most common skeletal complication of malignancy. Tumor cells disrupt normal bone remodeling to promote bone destruction and its associated morbidity. In the August 15, 2009, issue of Genes & Development, Lu and colleagues (pp. 1882-1894) propose a novel molecular mechanism by which tumor-produc...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.1854909
更新日期:2009-09-15 00:00:00
abstract::Previous studies have shown that differentiation of 3T3-L1 preadipocytes leads to the transcriptional activation of a group of adipose-specific genes. As an approach to defining the mechanism responsible for activating the expression of these genes, we investigated the binding of nuclear factors to the promoters of tw...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.9.1323
更新日期:1989-09-01 00:00:00
abstract::Numerous lines of study have suggested that the Hox genes, encoding putative transcription factors, are key genes in the establishment of the body plan of the mammalian embryo. To examine the role of Hoxa-5 (Hox1.3) gene during development, we have used targeted mutagenesis in embryonic stem cells to produce a strain ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.11.2085
更新日期:1993-11-01 00:00:00
abstract::The basic helix-loop-helix (bHLH) gene Hes7, a putative Notch effector, encodes a transcriptional repressor. Here, we found that Hes7 expression oscillates in 2-h cycles in the presomitic mesoderm (PSM). In Hes7-null mice, somites are not properly segmented and their anterior-posterior polarity is disrupted. As a resu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.930601
更新日期:2001-10-15 00:00:00
abstract::Nonsense-mediated mRNA decay (NMD) is a quality control mechanism that detects and degrades mRNAs containing premature stop codons (PTCs). In vertebrates, PTCs trigger efficient NMD when located upstream of an exon junction complex (EJC). Degradation of PTC-containing mRNAs requires the endonucleolytic activity of SMG...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.604610
更新日期:2010-11-01 00:00:00
abstract::Myocardial infarction and ischemic heart disease are the leading cause of death in the industrial world. Therapies employed for treating these diseases are aimed at promoting increased blood flow to cardiac tissue. Pharmacological induction of new coronary growth has recently been explored, however, clinical trials wi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1411406
更新日期:2006-06-15 00:00:00
abstract::SpoIIIE is an FtsK-related protein that transports the forespore chromosome across the Bacillus subtilis sporulation septum. We use membrane photobleaching and protoplast assays to demonstrate that SpoIIIE is required for septal membrane fission in the presence of trapped DNA, and that DNA is transported across separa...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1925210
更新日期:2010-06-01 00:00:00