Abstract：
:A chemicogenetic screen was performed in budding yeast mutants that have a weakened replication stress response. This identified an inhibitor of target of rapamycin (TOR) complexes 1 and 2 that selectively enhances the sensitivity of sgs1Δ cells to hydroxyurea and camptothecin. More importantly, the inhibitor has strong synthetic lethality in combination with either the break-inducing antibiotic Zeocin or ionizing radiation, independent of the strain background. Lethality correlates with a rapid fragmentation of chromosomes that occurs only when TORC2, but not TORC1, is repressed. Genetic inhibition of Tor2 kinase, or its downstream effector kinases Ypk1/Ypk2, conferred similar synergistic effects in the presence of Zeocin. Given that Ypk1/Ypk2 controls the actin cytoskeleton, we tested the effects of actin modulators latrunculin A and jasplakinolide. These phenocopy TORC2 inhibition on Zeocin, although modulation of calcineurin-sensitive transcription does not. These results implicate TORC2-mediated actin filament regulation in the survival of low levels of DNA damage.
journal_name
Mol Celljournal_title
Molecular cellauthors
Shimada K,Filipuzzi I,Stahl M,Helliwell SB,Studer C,Hoepfner D,Seeber A,Loewith R,Movva NR,Gasser SMdoi
10.1016/j.molcel.2013.08.019subject
Has Abstractpub_date
2013-09-26 00:00:00pages
829-39issue
6eissn
1097-2765issn
1097-4164pii
S1097-2765(13)00592-3journal_volume
51pub_type
杂志文章相关文献
MOLECULAR CELL文献大全abstract：:Anti-sense transcription originating upstream of mammalian protein-coding genes is a well-documented phenomenon, but remarkably little is known about the regulation or function of anti-sense promoters and the non-coding RNAs they generate. Here we define at nucleotide resolution the divergent transcription start sites...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2015.04.006
更新日期：2015-06-18 00:00:00
abstract：:Trimethylation on H3K27 (H3K27me3) mediated by Polycomb repressive complex 2 (PRC2) has been linked to embryonic stem cell (ESC) identity and pluripotency. EZH2, the catalytic subunit of PRC2, has been reported as the sole histone methyltransferase that methylates H3K27 and mediates transcriptional silencing. Analysis...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2008.10.016
更新日期：2008-11-21 00:00:00
abstract：:In a recent issue of Molecular Cell, Shiotani and Zou (2009) elucidate the biochemical mechanism underlying sequential ATM and ATR activation at DNA double-strand breaks, demonstrating that resection transforms ATM substrates into ATR substrates. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2009.03.004
更新日期：2009-03-27 00:00:00
abstract：:Folding-defective proteins must be cleared efficiently from the endoplasmic reticulum (ER) to prevent perturbation of the folding environment and to maintain cellular proteostasis. Misfolded proteins engage dislocation machineries (dislocons) built around E3 ubiquitin ligases that promote their transport across the ER...
journal_title：Molecular cell
pub_type： 杂志文章,收录出版
doi：10.1016/j.molcel.2013.10.016
更新日期：2013-12-26 00:00:00
abstract：:The proapoptotic Bcl-2 protein Bax is predominantly found in the cytosol of nonapoptotic cells and is commonly thought to translocate to mitochondria following an apoptotic stimulus. The current model for Bax activation is that BH3 proteins bind to cytosolic Bax, initiating mitochondrial targeting and outer-membrane p...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2012.12.022
更新日期：2013-03-07 00:00:00
abstract：:Ubiquitin-mediated proteolysis regulates the activity of diverse receptor systems. Here, we identify Smurf2, a C2-WW-HECT domain ubiquitin ligase and show that Smurf2 associates constitutively with Smad7. Smurf2 is nuclear, but binding to Smad7 induces export and recruitment to the activated TGF beta receptor, where i...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(00)00134-9
更新日期：2000-12-01 00:00:00
abstract：:N6-methyladenosine (m6A), the most abundant internal mRNA modification, and N6,2'-O-dimethyladenosine (m6Am), found at the first-transcribed nucleotide, are two reversible epitranscriptomic marks. However, the profiles and distribution patterns of m6A and m6Am across human and mouse tissues are poorly characterized. H...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2019.09.032
更新日期：2020-01-16 00:00:00
abstract：:tRNAs are subject to numerous modifications, including methylation. Mutations in the human N7-methylguanosine (m7G) methyltransferase complex METTL1/WDR4 cause primordial dwarfism and brain malformation, yet the molecular and cellular function in mammals is not well understood. We developed m7G methylated tRNA immunop...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2018.06.001
更新日期：2018-07-19 00:00:00
abstract：:Activation of NF-kappaB is regulated via numerous ubiquitin- and proteasome-mediated steps; an important one is processing of the precursor p105 to the p50 active subunit. The mechanisms involved are largely unknown, because this is an exceptional case where the ubiquitin system does not destroy its substrate complete...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2009.01.023
更新日期：2009-02-27 00:00:00
abstract：:Actin-related proteins (Arps) and conventional actin are enigmatic components of many chromatin-remodeling enzyme complexes. The yeast INO80 ATP-dependent chromatin-remodeling complex contains stoichiometric amounts of Arp4, Arp5, Arp8, and actin. Here we have revealed functions of Arp5 and Arp8 by analysis of mutants...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(03)00264-8
更新日期：2003-07-01 00:00:00
abstract：:Elucidating the individual and collaborative functions of genome maintenance factors is critical for understanding how genome duplication is achieved. Here, we investigate a conserved scaffold in budding yeast, Rtt107, and its three partners: a SUMO E3 complex, a ubiquitin E3 complex, and Slx4. Biochemical and genetic...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2015.08.023
更新日期：2015-10-15 00:00:00
abstract：:The binding of cytoplasmic proteins, such as talin, to the cytoplasmic domains of integrin adhesion receptors mediates bidirectional signal transduction. Here we report the crystal structure of the principal integrin binding and activating fragment of talin, alone and in complex with fragments of the beta 3 integrin t...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(02)00823-7
更新日期：2003-01-01 00:00:00
abstract：:R-loops, consisting of an RNA-DNA hybrid and displaced single-stranded DNA, are physiological structures that regulate various cellular processes occurring on chromatin. Intriguingly, changes in R-loop dynamics have also been associated with DNA damage accumulation and genome instability; however, the mechanisms under...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2014.10.020
更新日期：2014-12-18 00:00:00
abstract：:Two publications in the current issue of Cell introduce novel methods for high-throughput single-cell transcriptomics by using droplet microfluidics and sophisticated barcoding schemes for transcriptional profiling of thousands of individual cells. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2015.05.019
更新日期：2015-05-21 00:00:00
abstract：:We report the identification of histone PARylation factor 1 (HPF1; also known as C4orf27) as a regulator of ADP-ribosylation signaling in the DNA damage response. HPF1/C4orf27 forms a robust protein complex with PARP-1 in cells and is recruited to DNA lesions in a PARP-1-dependent manner, but independently of PARP-1 c...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2016.03.008
更新日期：2016-05-05 00:00:00
abstract：:Takahashi et al. (2018) report that the peptide CLE25 together with the BAM1, BAM3 LRR receptor-like kinases are involved in root-to-shoot communication during dehydration stress in Arabidopsis. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2018.06.011
更新日期：2018-06-21 00:00:00
abstract：:To determine whether replicational mutagenesis in the yeast genome is influenced by the positions of active origins, a reporter gene was placed in two orientations at multiple locations within a 39,000 bp region of chromosome III possessing two strong origins. The frequency of mutations resulting from misincorporation...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(02)00567-1
更新日期：2002-07-01 00:00:00
abstract：:Ubiquitin modification of proteins plays pivotal roles in the cellular response to DNA damage. Given the complexity of ubiquitin conjugation due to the formation of poly-conjugates of different linkages, functional roles of linkage-specific ubiquitin modification at DNA damage sites are largely unclear. We identify th...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2017.04.013
更新日期：2017-05-18 00:00:00
abstract：:Macroautophagy (autophagy) is a lysosome-dependent degradation process that has been implicated in age-associated diseases. Autophagy is involved in both cell survival and cell death, but little is known about the mechanisms that distinguish its use during these distinct cell fates. Here, we identify the microRNA miR-...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2014.09.011
更新日期：2014-11-06 00:00:00
abstract：:The RNA-binding protein HuR, while known to stabilize cytoplasmic mRNAs, is largely nuclear. In this issue of Molecular Cell, Mukherjee et al. (2011) and Lebedeva et al. (2011) identify transcriptome-wide HuR-RNA interactions using PAR-CLIP, unveiling HuR's nuclear role in pre-mRNA processing. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2011.07.016
更新日期：2011-08-05 00:00:00
abstract：:miRNAs are largely known to base pair with the 3'UTR of target mRNAs, downregulating their stability and translation. mRNA of betaTrCP1 ubiquitin ligase is very unstable, but unlike the majority of mRNAs where 3'UTR determines the rate of mRNA turnover, betaTrCP1 mRNA contains cis-acting destabilizing elements within ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2009.06.007
更新日期：2009-07-31 00:00:00
abstract：:BRAF is an oncogenic protein kinase that drives cell growth and proliferation through the MEK-ERK signaling pathway. BRAF inhibitors have demonstrated antitumor efficacy in melanoma therapy but have also been found to be associated with the development of cutaneous squamous cell carcinomas (cSCCs) in certain patients....
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2013.08.044
更新日期：2013-10-24 00:00:00
abstract：:It has been suspected that cell-cycle progression might be functionally coupled with RNA processing. However, little is known about the role of the precise splicing control in cell-cycle progression. Here, we report that SON, a large Ser/Arg (SR)-related protein, is a splicing cofactor contributing to efficient splici...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2011.03.014
更新日期：2011-04-22 00:00:00
abstract：:The duplication of eukaryotic genomes involves the replication of DNA from multiple origins of replication. In S phase, two sister replisomes assemble at each active origin, and they replicate DNA in opposite directions. Little is known about the functional relationship between sister replisomes. Some data imply that ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2010.11.027
更新日期：2010-12-10 00:00:00
abstract：:B cell CLL/lymphoma-2 (BCL-2) and its relatives comprise the BCL-2 family of proteins, which were originally characterized with respect to their roles in controlling outer mitochondrial membrane integrity and apoptosis. Current observations expand BCL-2 family function to include numerous cellular pathways. Here we wi...
journal_title：Molecular cell
pub_type： 杂志文章,评审
doi：10.1016/j.molcel.2010.01.025
更新日期：2010-02-12 00:00:00
abstract：:HAT1 is an essential gene in mammals that acetylates newly synthesized histone H4 and is involved in chromatin assembly and genome maintenance. In this issue of Molecular Cell, Gruber et al. (2019) show that HAT1 binds to and stimulates H4 gene expression in a growth-factor- and glucose-dependent manner. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2019.08.004
更新日期：2019-08-22 00:00:00
abstract：:Bursts of nascent mRNA have been shown to lead to substantial cell-cell variation in unicellular organisms, facilitating diverse responses to environmental challenges. It is unknown whether similar bursts and gene-expression noise occur in mammalian tissues. To address this, we combine single molecule transcript count...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2015.01.027
更新日期：2015-04-02 00:00:00
abstract：:The genomes of mammalian neurons contain uniquely high levels of non-CG DNA methylation that can be bound by the Rett syndrome protein, MeCP2, to regulate gene expression. How patterns of non-CG methylation are established in neurons and the mechanism by which this methylation works with MeCP2 to control gene expressi...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2019.10.033
更新日期：2020-01-16 00:00:00
abstract：:Inhibition of apoptotic response of host cells during an early phase of infection is a strategy used by many enteroinvasive bacterial pathogens to enhance their survival. Here, we report the identification of a soluble form of the pilus protein FimA from the culture supernatants of E. coli K1, Salmonella, and Shigella...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2010.02.015
更新日期：2010-03-26 00:00:00
abstract：:The histone methyltransferase PR-Set7/Set8 is the sole enzyme that catalyzes monomethylation of histone H4 at K20 (H4K20me1). Previous reports document disparate evidence regarding PR-Set7 expression during the cell cycle, the biological relevance of PR-Set7 interaction with PCNA, and its role in the cell. We find tha...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2010.10.011
更新日期：2010-11-12 00:00:00
