Abstract:
:S-phase cyclin-dependent kinase Cdc28-Clb5 (CDK-S) and Dbf4-dependent kinase Cdc7-Dbf4 (DDK) are highly conserved kinases well known for their roles in the initiation of DNA replication. CDK-S is also essential for initiation of meiotic recombination because it phosphorylates Ser30 of Mer2, a meiosis-specific double-strand break (DSB) protein. This work shows that the phosphorylation of Mer2 Ser30 by CDK-S primes Mer2 for subsequent phosphorylation by DDK on Ser29, creating a negatively charged "patch" necessary for DSB formation. CDK-S and DDK phosphorylation of Mer2 S30 and S29 can be bypassed by phosphomimetic amino acids, but break formation under these conditions is still dependent on DDK and CDK-S activity. Coordination between premeiotic S and DSB formation may be achieved by using CDK-S and DDK to initiate both processes. Many other proteins important for replication, recombination, repair, and chromosome segregation contain combination DDK/CDK sites, raising the possibility that this is a common regulatory mechanism.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Wan L,Niu H,Futcher B,Zhang C,Shokat KM,Boulton SJ,Hollingsworth NMdoi
10.1101/gad.1626408subject
Has Abstractpub_date
2008-02-01 00:00:00pages
386-97issue
3eissn
0890-9369issn
1549-5477pii
22/3/386journal_volume
22pub_type
杂志文章abstract::Atypical teratoid rhabdoid tumors (ATRTs) are challenging pediatric brain cancers that are predominantly associated with inactivation of the gene SMARCB1, a conserved subunit of the chromatin remodeling BAF complex, which has known contributions to developmental processes. To identify potential interactions between SM...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.339978.120
更新日期:2020-10-01 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::In Saccharomyces cerevisiae, the genes encoding the HO endonuclease, G1-specific cyclins CLN1 and CLN2, as well as most proteins involved in DNA synthesis, are periodically transcribed with maximal levels reached in late G1. For HO and the DNA replication genes, cell cycle stage-specific expression has been shown to b...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.4.557
更新日期:1992-04-01 00:00:00
abstract::The physiological functions of many vital tissues and organs continue to mature after birth, but the genetic mechanisms governing this postnatal maturation remain an unsolved mystery. Human pancreatic β cells produce and secrete insulin in response to physiological cues like glucose, and these hallmark functions impro...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.342378.120
更新日期:2021-01-14 00:00:00
abstract::Gut homeostasis is controlled by both immune and developmental mechanisms, and its disruption can lead to inflammatory disorders or cancerous lesions of the intestine. While the impact of bacteria on the mucosal immune system is beginning to be precisely understood, little is known about the effects of bacteria on gut...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1827009
更新日期:2009-10-01 00:00:00
abstract::Jun and Fos oncoproteins form a complex that regulates transcription from promoters containing AP-1 binding sites. The 'leucine zipper' domain of both Fos and Jun is necessary for the formation of the heterodimer, but the role of specific leucine residues is unclear. We have used site-specific mutagenesis to examine t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.6.770
更新日期:1989-06-01 00:00:00
abstract::Chromosomal processes related to formation and function of meiotic chiasmata have been analyzed in Sordaria macrospora. Double-strand breaks (DSBs), programmed or gamma-rays-induced, are found to promote four major events beyond recombination and accompanying synaptonemal complex formation: (1) juxtaposition of homolo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.275203
更新日期:2003-11-01 00:00:00
abstract::Multidimensional cancer genome analysis and validation has defined Quaking (QKI), a member of the signal transduction and activation of RNA (STAR) family of RNA-binding proteins, as a novel glioblastoma multiforme (GBM) tumor suppressor. Here, we establish that p53 directly regulates QKI gene expression, and QKI prote...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.189001.112
更新日期:2012-07-01 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 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::DNA repair associated with DNA replication is important for the conservation of genomic sequence information, whereas reconstitution of chromatin after replication sustains epigenetic information. We have isolated and characterized mutations in the BRU1 gene of Arabidopsis that suggest a novel link between these under...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.295404
更新日期:2004-04-01 00:00:00
abstract::The SNF1 protein kinase is broadly conserved in eukaryotes and has been implicated in responses to environmental and nutritional stress. In yeast, the SNF1 kinase has a central role in the response to glucose starvation. SNF1 is associated with its activating subunit, SNF4, and other proteins in complexes. Using the t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.24.3105
更新日期:1996-12-15 00:00:00
abstract::How RNA-binding proteins recognize specific sets of target mRNAs remains poorly understood because current approaches depend primarily on sequence information. In this study, we demonstrate that specific recognition of messenger RNAs (mRNAs) by RNA-binding proteins requires the correct spatial positioning of these seq...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.177428.111
更新日期:2012-01-01 00:00:00
abstract::Actin is associated with all three nuclear RNA polymerases and acts in concert with nuclear myosin I (NM1) to drive transcription. Practically nothing is known regarding the state of actin and the functional interplay of actin and NM1 in transcription. Here we show that actin and NM1 act in concert to promote RNA poly...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.455908
更新日期:2008-02-01 00:00:00
abstract::The transcription factor NF-kappaB is a critical regulator of inflammatory and cell survival signals. Proteasomal degradation of NF-kappaB subunits plays an important role in the termination of NF-kappaB activity, and at least one of the identified ubiquitin ligases is a multimeric complex containing Copper Metabolism...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1748409
更新日期:2009-04-01 00:00:00
abstract::U4 and U6 small nuclear RNAs are associated by an extensive base-pairing interaction that must be disrupted and reformed with each round of splicing. U4 mutations within the U4/U6 interaction domain destabilize the complex in vitro and cause a cold-sensitive phenotype in vivo. Restabilization of the U4/U6 helix by dom...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.5.773
更新日期:1991-05-01 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::We characterized a gene, extradenticle, which seems to interact with a specific subset of Drosophila homeo domain proteins, possibly affecting their target specificity. This interpretation is based on an examination of the zygotic and maternal effect phenotypes of extradenticle mutations. In embryos with reduced level...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.7.1209
更新日期:1990-07-01 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::The reelin (reln) and disabled 1 (dab1) genes both ensure correct neuronal positioning during brain development. We have found that the intracellular Dab1 protein receives a tyrosine phosphorylation signal from extracellular Reln protein. Genetic analysis shows that reln function depends on dab1, and vice versa, as ex...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.6.643
更新日期:1999-03-15 00:00:00
abstract::Translation of encephalomyocarditis virus (EMCV) mRNA occurs by ribosomal internal entry into the 5'-nontranslated region (5' NTR) rather than by ribosomal scanning. The internal ribosomal entry site (IRES) in the EMCV 5' NTR was determined by in vitro translation with RNAs that were generated by in vitro transcriptio...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.9.1560
更新日期:1990-09-01 00:00:00
abstract::SET8 (also known as PR-SET7) is a histone H4-Lys-20-specific methyltransferase that is implicated in cell-cycle-dependent transcriptional silencing and mitotic regulation in metazoans. Herein we report the crystal structure of human SET8 (hSET8) bound to a histone H4 peptide bearing Lys-20 and the product cofactor S-a...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1318405
更新日期:2005-06-15 00:00:00
abstract::The subdivision of the Drosophila body into distinct terminal and central domains depends on the torso (tor) protein, a putative receptor tyrosine kinase that is active at both ends of the early embryo. We show that the tor protein is uniformly expressed along the surface membrane of early embryos despite its localize...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.12b.2025
更新日期:1989-12-01 00:00:00
abstract::The distal enhancer of the T-cell receptor (TCR) alpha chain gene has become a paradigm for studies of the assembly and activity of architectural enhancer complexes. Here we have reconstituted regulated TCR alpha enhancer activity in vitro on chromatin templates using purified T-cell transcription factors (LEF-1, AML1...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.7.887
更新日期:1997-04-01 00:00:00
abstract::Cells have evolved checkpoint responses to arrest or delay the cell cycle, activate DNA repair networks, or induce apoptosis after genomic perturbation. Cells have also evolved the translesion synthesis processes to tolerate genomic lesions by either error-free or error-prone repair. Here, we show that after a replica...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1043203
更新日期:2003-01-01 00:00:00
abstract::Accurate completion of replication relies on the ability of cells to activate error-free recombination-mediated DNA damage bypass at sites of perturbed replication. However, as anti-recombinase activities are also recruited to replication forks, how recombination-mediated damage bypass is enabled at replication stress...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.265629.115
更新日期:2015-10-01 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::Genomic imprinting is an epigenetic phenomenon leading to parentally biased gene expression. Throughout the years, extensive efforts have been made to characterize the epigenetic marks underlying imprinting in animals and plants. As a result, DNA methylation asymmetries between parental genomes emerged as the primary ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.332924.119
更新日期:2020-01-01 00:00:00
abstract::Alternative polyadenylation (APA) is widespread in neuronal development and activity-mediated neural plasticity. However, the underlying molecular mechanisms are largely unknown. We used systematic genetic studies and genome-wide surveys of the transcriptional landscape to identify a context-dependent regulatory pathw...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.266650.115
更新日期:2015-11-15 00:00:00
abstract::Two recent reports, including one by Reinders and colleagues (pp. 939-950) in the April 15, 2009, issue of Genes & Development, describe the construction of Arabidopsis recombinant inbred populations that maximize epigenetic rather than genetic variation. The distribution and behavior of phenotypic variation in these ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1824909
更新日期:2009-07-15 00:00:00