Abstract:
:Copy-number changes generate phenotypic variability in health and disease. Whether organisms protect against copy-number changes is largely unknown. Here, we show that Saccharomyces cerevisiae monitors the copy number of its ribosomal DNA (rDNA) and rapidly responds to copy-number loss with the clonal amplification of extrachromosomal rDNA circles (ERCs) from chromosomal repeats. ERC formation is replicative, separable from repeat loss, and reaches a dynamic steady state that responds to the addition of exogenous rDNA copies. ERC levels are also modulated by RNAPI activity and diet, suggesting that rDNA copy number is calibrated against the cellular demand for rRNA. Last, we show that ERCs reinsert into the genome in a dosage-dependent manner, indicating that they provide a reservoir for ultimately increasing rDNA array length. Our results reveal a DNA-based mechanism for rapidly restoring copy number in response to catastrophic gene loss that shares fundamental features with unscheduled copy-number amplifications in cancer cells.
journal_name
Mol Celljournal_title
Molecular cellauthors
Mansisidor A,Molinar T Jr,Srivastava P,Dartis DD,Pino Delgado A,Blitzblau HG,Klein H,Hochwagen Adoi
10.1016/j.molcel.2018.08.036subject
Has Abstractpub_date
2018-11-01 00:00:00pages
583-593.e4issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(18)30696-8journal_volume
72pub_type
杂志文章相关文献
MOLECULAR CELL文献大全abstract::Pre-mRNA splicing relies on the poorly understood dynamic interplay between >150 protein components of the spliceosome. The steps at which splicing can be regulated remain largely unknown. We systematically analyzed the effect of knocking down the components of the splicing machinery on alternative splicing events rel...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2014.10.030
更新日期:2015-01-08 00:00:00
abstract::Alternative splicing (AS) generates isoform diversity for cellular identity and homeostasis in multicellular life. Although AS variation has been observed among single cells, little is known about the biological or evolutionary significance of such variation. We developed Expedition, a computational framework consisti...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2017.06.003
更新日期:2017-07-06 00:00:00
abstract::Concomitant with DNA replication, the chromosomal cohesin complex establishes cohesion between newly replicated sister chromatids. Several replication-fork-associated "cohesion establishment factors," including the multifunctional Ctf18-RFC complex, aid this process in as yet unknown ways. Here, we show that Ctf18-RFC...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2020.03.017
更新日期:2020-05-21 00:00:00
abstract::Recent work from Kuehner and Brow (2008) and Thiebaut et al. (2008) in Molecular Cell and Jenks et al. (2008) in Molecular and Cellular Biology reveals that regulated expression of central nucleotide synthesis pathway components directs start site-dependent RNA polymerase II termination. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2008.08.014
更新日期:2008-09-05 00:00:00
abstract::Trimethylation of histone H3 on lysine 4 (H3K4me3) localizes near the 5' region of genes and is tightly associated with active loci. Several proteins, such as CHD1, BPTF, JMJD2A, and the ING tumor suppressor family, directly recognize this lysine methyl mark. However, how H3K4me3 recognition participates in active tra...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2007.11.010
更新日期:2007-11-30 00:00:00
abstract::The small nuclear RNA (snRNA) genes have been widely used as a model system for understanding transcriptional regulation due to the unique aspects of their promoter structure, selectivity for either RNA polymerase (Pol) II or III, and because of their unique mechanism of termination that is tightly linked with the pro...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2013.07.003
更新日期:2013-08-22 00:00:00
abstract::An exciting study in this issue reveals how binding of the microtubule associated protein TPX2 to the mitotic kinase Aurora A induces a conformational change. This moves the phosphorylated activation domain into a more compact position within the kinase core, providing a better substrate binding platform and hiding th...
journal_title:Molecular cell
pub_type: 评论,杂志文章,评审
doi:10.1016/s1097-2765(03)00405-2
更新日期:2003-10-01 00:00:00
abstract::Faithful copying of the genome is essential for life. In eukaryotes, a single archaeo-eukaryotic primase (AEP), DNA primase, is required for the initiation and progression of DNA replication. Here we have identified additional eukaryotic AEP-like proteins with DNA-dependent primase and/or polymerase activity. Uniquely...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2013.10.034
更新日期:2013-11-21 00:00:00
abstract::Cardozo Gizzi et al. (2019) develop a new sequential imaging methodology (Hi-M) for observing chromosome structure in the Drosophila blastoderm and find that topological domains in single nuclei change in response to transcriptional activation. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2019.03.017
更新日期:2019-04-04 00:00:00
abstract::RNA-mediated gene silencing in human cells requires the accurate generation of ∼22 nt microRNAs (miRNAs) from double-stranded RNA substrates by the endonuclease Dicer. Although the phylogenetically conserved RNA-binding proteins TRBP and PACT are known to contribute to this process, their mode of Dicer binding and the...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2014.11.030
更新日期:2015-02-05 00:00:00
abstract::R loop, a transcription intermediate containing RNA:DNA hybrids and displaced single-stranded DNA (ssDNA), has emerged as a major source of genomic instability. RNaseH1, which cleaves the RNA in RNA:DNA hybrids, plays an important role in R loop suppression. Here we show that replication protein A (RPA), an ssDNA-bind...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2017.01.029
更新日期:2017-03-02 00:00:00
abstract::In this issue, Takahara and Maeda (2012) discover that together, Pbp1 and sequestration of the TORC1 complex in cytoplasmic mRNP stress granules provides a negative regulatory mechanism for TORC1 signaling during stress. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2012.07.005
更新日期:2012-07-27 00:00:00
abstract::Thousands of cis-elements in genomes are predicted to have vital functions. Although conservation, activity in surrogate assays, polymorphisms, and disease mutations provide functional clues, deletion from endogenous loci constitutes the gold-standard test. A GATA-2-binding, Gata2 intronic cis-element (+9.5) required ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2015.05.020
更新日期:2015-07-02 00:00:00
abstract::Microtubule plus end binding proteins (+TIPs) localize to the dynamic plus ends of microtubules, where they stimulate microtubule growth and recruit signaling molecules. Three main +TIP classes have been identified (XMAP215, EB1, and CLIP-170), but whether they act upon microtubule plus ends through a similar mechanis...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2007.07.023
更新日期:2007-09-21 00:00:00
abstract::Using Micro-C, Hsieh et al. (2020) and Krietenstein et al. (2020) investigated 3D chromatin folding in human and mouse cells at unprecedented resolution to uncover ultra-fine-scale chromatin structures that provide direct links between genome architecture, gene expression, and gene regulation. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2020.04.021
更新日期:2020-05-07 00:00:00
abstract::ADP-ribosylation is a post-translational modification where single units (mono-ADP-ribosylation) or polymeric chains (poly-ADP-ribosylation) of ADP-ribose are conjugated to proteins by ADP-ribosyltransferases. This post-translational modification and the ADP-ribosyltransferases (also known as PARPs) responsible for it...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2015.06.012
更新日期:2015-06-18 00:00:00
abstract::Spt6 is an essential histone chaperone that mediates nucleosome reassembly during gene transcription. Spt6 also associates with RNA polymerase II (RNAPII) via a tandem Src2 homology domain. However, the significance of Spt6-RNAPII interaction is not well understood. Here, we show that Spt6 recruitment to genes and the...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2018.05.020
更新日期:2018-06-21 00:00:00
abstract::Autophagy is required for benign hepatic tumors to progress into malignant hepatocellular carcinoma. However, the mechanism is unclear. Here, we report that mitophagy, the selective removal of mitochondria by autophagy, positively regulates hepatic cancer stem cells (CSCs) by suppressing the tumor suppressor p53. When...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2017.09.022
更新日期:2017-10-19 00:00:00
abstract::Alternative lengthening of telomeres (ALT) is a homology-directed repair (HDR) mechanism of telomere elongation that controls proliferation in aggressive cancers. We show that the disruption of RAD51-associated protein 1 (RAD51AP1) in ALT+ cancer cells leads to generational telomere shortening. This is due to RAD51AP1...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2019.06.043
更新日期:2019-10-03 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::Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2014.03.021
更新日期:2014-05-08 00:00:00
abstract::Sister-chromatid cohesion describes the orderly association of newly replicated DNA molecules behind replication forks. It plays an essential role in the maintenance and faithful transmission of genetic information. Cohesion is created by DNA topological links and proteinaceous bridges, whose formation and deposition ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2020.06.033
更新日期:2020-09-03 00:00:00
abstract::Mutation and prevalence of pathogenic viruses prompt the development of broad-spectrum antiviral strategies. Viperin is a potent antiviral protein that inhibits a broad range of viruses. Unexpectedly, we found that Viperin protein production in epithelium is defective in response to both viruses and interferons (IFNs)...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2019.11.003
更新日期:2020-02-20 00:00:00
abstract::Glycogen is the major mammalian glucose storage cache and is critical for energy homeostasis. Glycogen synthesis in neurons must be tightly controlled due to neuronal sensitivity to perturbations in glycogen metabolism. Lafora disease (LD) is a fatal, congenital, neurodegenerative epilepsy. Mutations in the gene encod...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2014.11.020
更新日期:2015-01-22 00:00:00
abstract::Recycling of RNA polymerase II (Pol II) after transcription requires dephosphorylation of the polymerase C-terminal domain (CTD) by the phosphatase Fcp1. We report the X-ray structure of the small CTD phosphatase Scp1, which is homologous to the Fcp1 catalytic domain. The structure shows a core fold and an active cent...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2004.06.035
更新日期:2004-08-13 00:00:00
abstract::The signal transducers of the transforming growth factor beta (TGFbeta)/bone morphogenetic protein (BMP), the Smads, promote the expression of a subset of miRNAs by facilitating the cleavage reaction by Drosha. The mechanism that limits Smad-mediated processing to a selective group of miRNAs remained hitherto unexplor...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2010.07.011
更新日期:2010-08-13 00:00:00
abstract::While gapmers efficiently knock down as well as terminate transcription of nascent lncRNAs and mRNAs, Lee and Mendell (2020) and Lai et al. (2020) also demonstrate that Pol II termination is not observed with gapmers targeting the 3' terminal portions of the transcript. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2020.02.010
更新日期:2020-03-05 00:00:00
abstract::The exosome plays key roles in RNA maturation and surveillance, but it is unclear how target RNAs are identified. We report the functional characterization of the yeast exosome component Rrp44, a member of the RNase II family. Recombinant Rrp44 and the purified TRAMP polyadenylation complex each specifically recognize...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2007.06.006
更新日期:2007-07-20 00:00:00
abstract::Perfringolysin O, a bacterial cytolytic toxin, forms unusually large pores in cholesterol-containing membranes by the spontaneous insertion of two of its four domains into the bilayer. By monitoring the kinetics of domain-specific conformational changes and pore formation using fluorescence spectroscopy, the temporal ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)00119-2
更新日期:2000-11-01 00:00:00
abstract::The tumor suppressor protein, p53, plays a critical role in mediating cellular response to stress signals by regulating genes involved in cell cycle arrest and apoptosis. p53 is believed to be inactive for DNA binding unless its C terminus is modified or structurally altered. We show that unmodified p53 actively binds...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(01)00283-0
更新日期:2001-07-01 00:00:00