Proteins in the nutrient-sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage.

Abstract:

:Checkpoint pathways regulate genomic integrity in part by blocking anaphase until all chromosomes have been completely replicated, repaired, and correctly aligned on the spindle. In Saccharomyces cerevisiae, DNA damage and mono-oriented or unattached kinetochores trigger checkpoint pathways that bifurcate to regulate both the metaphase to anaphase transition and mitotic exit. The sensor-associated kinase, Mec1, phosphorylates two downstream kinases, Chk1 and Rad53. Activation of Chk1 and Rad53 prevents anaphase and causes inhibition of the mitotic exit network. We have previously shown that the PKA pathway plays a role in blocking securin and Clb2 destruction following DNA damage. Here we show that the Mec1 DNA damage checkpoint regulates phosphorylation of the regulatory (R) subunit of PKA following DNA damage and that the phosphorylated R subunit has a role in restraining mitosis following DNA damage. In addition we found that proteins known to regulate PKA in response to nutrients and stress either by phosphorylation of the R subunit or regulating levels of cAMP are required for the role of PKA in the DNA damage checkpoint. Our data indicate that there is cross-talk between the DNA damage checkpoint and the proteins that integrate nutrient and stress signals to regulate PKA.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Searle JS,Wood MD,Kaur M,Tobin DV,Sanchez Y

doi

10.1371/journal.pgen.1002176

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

e1002176

issue

7

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-11-00030

journal_volume

7

pub_type

杂志文章
  • Tcf7 is an important regulator of the switch of self-renewal and differentiation in a multipotential hematopoietic cell line.

    abstract::A critical problem in biology is understanding how cells choose between self-renewal and differentiation. To generate a comprehensive view of the mechanisms controlling early hematopoietic precursor self-renewal and differentiation, we used systems-based approaches and murine EML multipotential hematopoietic precursor...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002565

    authors: Wu JQ,Seay M,Schulz VP,Hariharan M,Tuck D,Lian J,Du J,Shi M,Ye Z,Gerstein M,Snyder MP,Weissman S

    更新日期:2012-01-01 00:00:00

  • Genetic analysis of floral symmetry in Van Gogh's sunflowers reveals independent recruitment of CYCLOIDEA genes in the Asteraceae.

    abstract::The genetic basis of floral symmetry is a topic of great interest because of its effect on pollinator behavior and, consequently, plant diversification. The Asteraceae, which is the largest family of flowering plants, is an ideal system in which to study this trait, as many species within the family exhibit a compound...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002628

    authors: Chapman MA,Tang S,Draeger D,Nambeesan S,Shaffer H,Barb JG,Knapp SJ,Burke JM

    更新日期:2012-01-01 00:00:00

  • Canonical Poly(A) Polymerase Activity Promotes the Decay of a Wide Variety of Mammalian Nuclear RNAs.

    abstract::The human nuclear poly(A)-binding protein PABPN1 has been implicated in the decay of nuclear noncoding RNAs (ncRNAs). In addition, PABPN1 promotes hyperadenylation by stimulating poly(A)-polymerases (PAPα/γ), but this activity has not previously been linked to the decay of endogenous transcripts. Moreover, the mechani...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005610

    authors: Bresson SM,Hunter OV,Hunter AC,Conrad NK

    更新日期:2015-10-20 00:00:00

  • Imputation of canine genotype array data using 365 whole-genome sequences improves power of genome-wide association studies.

    abstract::Genomic resources for the domestic dog have improved with the widespread adoption of a 173k SNP array platform and updated reference genome. SNP arrays of this density are sufficient for detecting genetic associations within breeds but are underpowered for finding associations across multiple breeds or in mixed-breed ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008003

    authors: Hayward JJ,White ME,Boyle M,Shannon LM,Casal ML,Castelhano MG,Center SA,Meyers-Wallen VN,Simpson KW,Sutter NB,Todhunter RJ,Boyko AR

    更新日期:2019-09-16 00:00:00

  • The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia.

    abstract::Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two spec...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005493

    authors: Muñoz JF,Gauthier GM,Desjardins CA,Gallo JE,Holder J,Sullivan TD,Marty AJ,Carmen JC,Chen Z,Ding L,Gujja S,Magrini V,Misas E,Mitreva M,Priest M,Saif S,Whiston EA,Young S,Zeng Q,Goldman WE,Mardis ER,Taylor JW,Mc

    更新日期:2015-10-06 00:00:00

  • Cell size checkpoint control by the retinoblastoma tumor suppressor pathway.

    abstract::Size control is essential for all proliferating cells, and is thought to be regulated by checkpoints that couple cell size to cell cycle progression. The aberrant cell-size phenotypes caused by mutations in the retinoblastoma (RB) tumor suppressor pathway are consistent with a role in size checkpoint control, but indi...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0020167

    authors: Fang SC,de los Reyes C,Umen JG

    更新日期:2006-10-13 00:00:00

  • Recovery of novel association loci in Arabidopsis thaliana and Drosophila melanogaster through leveraging INDELs association and integrated burden test.

    abstract::Short insertions, deletions (INDELs) and larger structural variants have been increasingly employed in genetic association studies, but few improvements over SNP-based association have been reported. In order to understand why this might be the case, we analysed two publicly available datasets and observed that 63% of...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007699

    authors: Song B,Mott R,Gan X

    更新日期:2018-10-16 00:00:00

  • PNUTS/PP1 regulates RNAPII-mediated gene expression and is necessary for developmental growth.

    abstract::In multicellular organisms, tight regulation of gene expression ensures appropriate tissue and organismal growth throughout development. Reversible phosphorylation of the RNA Polymerase II (RNAPII) C-terminal domain (CTD) is critical for the regulation of gene expression states, but how phosphorylation is actively mod...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003885

    authors: Ciurciu A,Duncalf L,Jonchere V,Lansdale N,Vasieva O,Glenday P,Rudenko A,Vissi E,Cobbe N,Alphey L,Bennett D

    更新日期:2013-10-01 00:00:00

  • BOD1 Is Required for Cognitive Function in Humans and Drosophila.

    abstract::Here we report a stop-mutation in the BOD1 (Biorientation Defective 1) gene, which co-segregates with intellectual disability in a large consanguineous family, where individuals that are homozygous for the mutation have no detectable BOD1 mRNA or protein. The BOD1 protein is required for proper chromosome segregation,...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006022

    authors: Esmaeeli-Nieh S,Fenckova M,Porter IM,Motazacker MM,Nijhof B,Castells-Nobau A,Asztalos Z,Weißmann R,Behjati F,Tzschach A,Felbor U,Scherthan H,Sayfati SM,Ropers HH,Kahrizi K,Najmabadi H,Swedlow JR,Schenck A,Kuss AW

    更新日期:2016-05-11 00:00:00

  • Unexpected cancer-predisposition gene variants in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome patients without underlying germline PTEN mutations.

    abstract::Patients with heritable cancer syndromes characterized by germline PTEN mutations (termed PTEN hamartoma tumor syndrome, PHTS) benefit from PTEN-enabled cancer risk assessment and clinical management. PTEN-wildtype patients (~50%) remain at increased risk of developing certain cancers. Existence of germline mutations ...

    journal_title:PLoS genetics

    pub_type: 杂志文章,多中心研究

    doi:10.1371/journal.pgen.1007352

    authors: Yehia L,Ni Y,Sesock K,Niazi F,Fletcher B,Chen HJL,LaFramboise T,Eng C

    更新日期:2018-04-23 00:00:00

  • A drastic reduction in the life span of cystatin C L68Q carriers due to life-style changes during the last two centuries.

    abstract::Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disease with high penetrance, manifest by brain hemorrhages in young normotensive adults. In Iceland, this condition is caused by the L68Q mutation in the cystatin C gene, with contemporary carriers reaching an average age of only 30 years. Here...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000099

    authors: Palsdottir A,Helgason A,Palsson S,Bjornsson HT,Bragason BT,Gretarsdottir S,Thorsteinsdottir U,Olafsson E,Stefansson K

    更新日期:2008-06-20 00:00:00

  • East-Asian Helicobacter pylori strains synthesize heptan-deficient lipopolysaccharide.

    abstract::The lipopolysaccharide O-antigen structure expressed by the European Helicobacter pylori model strain G27 encompasses a trisaccharide, an intervening glucan-heptan and distal Lewis antigens that promote immune escape. However, several gaps still remain in the corresponding biosynthetic pathway. Here, systematic mutage...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008497

    authors: Li H,Marceau M,Yang T,Liao T,Tang X,Hu R,Xie Y,Tang H,Tay A,Shi Y,Shen Y,Yang T,Pi X,Lamichhane B,Luo Y,Debowski AW,Nilsson HO,Haslam SM,Mulloy B,Dell A,Stubbs KA,Marshall BJ,Benghezal M

    更新日期:2019-11-20 00:00:00

  • Inflammation-mediated genetic and epigenetic alterations drive cancer development in the neighboring epithelium upon stromal abrogation of TGF-β signaling.

    abstract::Deletion of tumor suppressor genes in stromal fibroblasts induces epithelial cancer development, suggesting an important role of stroma in epithelial homoeostasis. However, the underlying mechanisms remain to be elucidated. Here we report that deletion of the gene encoding TGFβ receptor 2 (Tgfbr2) in the stromal fibro...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003251

    authors: Achyut BR,Bader DA,Robles AI,Wangsa D,Harris CC,Ried T,Yang L

    更新日期:2013-01-01 00:00:00

  • Arabidopsis thaliana chromosome 4 replicates in two phases that correlate with chromatin state.

    abstract::DNA replication programs have been studied extensively in yeast and animal systems, where they have been shown to correlate with gene expression and certain epigenetic modifications. Despite the conservation of core DNA replication proteins, little is known about replication programs in plants. We used flow cytometry ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000982

    authors: Lee TJ,Pascuzzi PE,Settlage SB,Shultz RW,Tanurdzic M,Rabinowicz PD,Menges M,Zheng P,Main D,Murray JA,Sosinski B,Allen GC,Martienssen RA,Hanley-Bowdoin L,Vaughn MW,Thompson WF

    更新日期:2010-06-10 00:00:00

  • Regulation of Neurod1 contributes to the lineage potential of Neurogenin3+ endocrine precursor cells in the pancreas.

    abstract::During pancreatic development, transcription factor cascades gradually commit precursor populations to the different endocrine cell fate pathways. Although mutational analyses have defined the functions of many individual pancreatic transcription factors, the integrative transcription factor networks required to regul...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003278

    authors: Mastracci TL,Anderson KR,Papizan JB,Sussel L

    更新日期:2013-01-01 00:00:00

  • Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity.

    abstract::Replicative DNA helicases expose the two strands of the double helix to the replication apparatus, but accessory helicases are often needed to help forks move past naturally occurring hard-to-replicate sites, such as tightly bound proteins, RNA/DNA hybrids, and DNA secondary structures. Although the Schizosaccharomyce...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006238

    authors: McDonald KR,Guise AJ,Pourbozorgi-Langroudi P,Cristea IM,Zakian VA,Capra JA,Sabouri N

    更新日期:2016-09-09 00:00:00

  • Unraveling the regulatory mechanisms underlying tissue-dependent genetic variation of gene expression.

    abstract::It is known that genetic variants can affect gene expression, but it is not yet completely clear through what mechanisms genetic variation mediate this expression. We therefore compared the cis-effect of single nucleotide polymorphisms (SNPs) on gene expression between blood samples from 1,240 human subjects and four ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002431

    authors: Fu J,Wolfs MG,Deelen P,Westra HJ,Fehrmann RS,Te Meerman GJ,Buurman WA,Rensen SS,Groen HJ,Weersma RK,van den Berg LH,Veldink J,Ophoff RA,Snieder H,van Heel D,Jansen RC,Hofker MH,Wijmenga C,Franke L

    更新日期:2012-01-01 00:00:00

  • Introns regulate gene expression in Cryptococcus neoformans in a Pab2p dependent pathway.

    abstract::Most Cryptococccus neoformans genes are interrupted by introns, and alternative splicing occurs very often. In this study, we examined the influence of introns on C. neoformans gene expression. For most tested genes, elimination of introns greatly reduces mRNA accumulation. Strikingly, the number and the position of i...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003686

    authors: Goebels C,Thonn A,Gonzalez-Hilarion S,Rolland O,Moyrand F,Beilharz TH,Janbon G

    更新日期:2013-01-01 00:00:00

  • Loss of Xist RNA from the inactive X during B cell development is restored in a dynamic YY1-dependent two-step process in activated B cells.

    abstract::X-chromosome inactivation (XCI) in female lymphocytes is uniquely regulated, as the inactive X (Xi) chromosome lacks localized Xist RNA and heterochromatin modifications. Epigenetic profiling reveals that Xist RNA is lost from the Xi at the pro-B cell stage and that additional heterochromatic modifications are gradual...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007050

    authors: Syrett CM,Sindhava V,Hodawadekar S,Myles A,Liang G,Zhang Y,Nandi S,Cancro M,Atchison M,Anguera MC

    更新日期:2017-10-09 00:00:00

  • High-resolution mapping of expression-QTLs yields insight into human gene regulation.

    abstract::Recent studies of the HapMap lymphoblastoid cell lines have identified large numbers of quantitative trait loci for gene expression (eQTLs). Reanalyzing these data using a novel Bayesian hierarchical model, we were able to create a surprisingly high-resolution map of the typical locations of sites that affect mRNA lev...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000214

    authors: Veyrieras JB,Kudaravalli S,Kim SY,Dermitzakis ET,Gilad Y,Stephens M,Pritchard JK

    更新日期:2008-10-01 00:00:00

  • Positive selection for new disease mutations in the human germline: evidence from the heritable cancer syndrome multiple endocrine neoplasia type 2B.

    abstract::Multiple endocrine neoplasia type 2B (MEN2B) is a highly aggressive thyroid cancer syndrome. Since almost all sporadic cases are caused by the same nucleotide substitution in the RET proto-oncogene, the calculated disease incidence is 100-200 times greater than would be expected based on the genome average mutation fr...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002420

    authors: Choi SK,Yoon SR,Calabrese P,Arnheim N

    更新日期:2012-01-01 00:00:00

  • Fpr1, a primary target of rapamycin, functions as a transcription factor for ribosomal protein genes cooperatively with Hmo1 in Saccharomyces cerevisiae.

    abstract::Fpr1 (FK506-sensitive proline rotamase 1), a protein of the FKBP12 (FK506-binding protein 12 kDa) family in Saccharomyces cerevisiae, is a primary target for the immunosuppressive agents FK506 and rapamycin. Fpr1 inhibits calcineurin and TORC1 (target of rapamycin complex 1) when bound to FK506 and rapamycin, respecti...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008865

    authors: Kasahara K,Nakayama R,Shiwa Y,Kanesaki Y,Ishige T,Yoshikawa H,Kokubo T

    更新日期:2020-06-30 00:00:00

  • A role for E2F activities in determining the fate of Myc-induced lymphomagenesis.

    abstract::The phenotypic heterogeneity that characterizes human cancers reflects the enormous genetic complexity of the oncogenic process. This complexity can also be seen in mouse models where it is frequently observed that in addition to the initiating genetic alteration, the resulting tumor harbors additional, somatically ac...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000640

    authors: Rempel RE,Mori S,Gasparetto M,Glozak MA,Andrechek ER,Adler SB,Laakso NM,Lagoo AS,Storms R,Smith C,Nevins JR

    更新日期:2009-09-01 00:00:00

  • The Homeodomain Iroquois Proteins Control Cell Cycle Progression and Regulate the Size of Developmental Fields.

    abstract::During development, proper differentiation and final organ size rely on the control of territorial specification and cell proliferation. Although many regulators of these processes have been identified, how both are coordinated remains largely unknown. The homeodomain Iroquois/Irx proteins play a key, evolutionarily c...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005463

    authors: Barrios N,González-Pérez E,Hernández R,Campuzano S

    更新日期:2015-08-25 00:00:00

  • A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus.

    abstract::Generally, the second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiate...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006080

    authors: Skotnicka D,Smaldone GT,Petters T,Trampari E,Liang J,Kaever V,Malone JG,Singer M,Søgaard-Andersen L

    更新日期:2016-05-23 00:00:00

  • The Regulatory T Cell Lineage Factor Foxp3 Regulates Gene Expression through Several Distinct Mechanisms Mostly Independent of Direct DNA Binding.

    abstract::The lineage factor Foxp3 is essential for the development and maintenance of regulatory T cells, but little is known about the mechanisms involved. Here, we demonstrate that an N-terminal proline-rich interaction region is crucial for Foxp3's function. Subdomains within this key region link Foxp3 to several independen...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005251

    authors: Xie X,Stubbington MJ,Nissen JK,Andersen KG,Hebenstreit D,Teichmann SA,Betz AG

    更新日期:2015-06-24 00:00:00

  • Transcriptome-wide mapping of 5-methylcytidine RNA modifications in bacteria, archaea, and yeast reveals m5C within archaeal mRNAs.

    abstract::The presence of 5-methylcytidine (m(5)C) in tRNA and rRNA molecules of a wide variety of organisms was first observed more than 40 years ago. However, detection of this modification was limited to specific, abundant, RNA species, due to the usage of low-throughput methods. To obtain a high resolution, systematic, and ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003602

    authors: Edelheit S,Schwartz S,Mumbach MR,Wurtzel O,Sorek R

    更新日期:2013-06-01 00:00:00

  • Nonsense-mediated decay enables intron gain in Drosophila.

    abstract::Intron number varies considerably among genomes, but despite their fundamental importance, the mutational mechanisms and evolutionary processes underlying the expansion of intron number remain unknown. Here we show that Drosophila, in contrast to most eukaryotic lineages, is still undergoing a dramatic rate of intron ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000819

    authors: Farlow A,Meduri E,Dolezal M,Hua L,Schlötterer C

    更新日期:2010-01-22 00:00:00

  • RNA-processing protein TDP-43 regulates FOXO-dependent protein quality control in stress response.

    abstract::Protein homeostasis is critical for cell survival and functions during stress and is regulated at both RNA and protein levels. However, how the cell integrates RNA-processing programs with post-translational protein quality control systems is unknown. Transactive response DNA-binding protein (TARDBP/TDP-43) is an RNA-...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004693

    authors: Zhang T,Baldie G,Periz G,Wang J

    更新日期:2014-10-16 00:00:00

  • Next-generation sequencing identifies the Danforth's short tail mouse mutation as a retrotransposon insertion affecting Ptf1a expression.

    abstract::The semidominant Danforth's short tail (Sd) mutation arose spontaneously in the 1920s. The homozygous Sd phenotype includes severe malformations of the axial skeleton with an absent tail, kidney agenesis, anal atresia, and persistent cloaca. The Sd mutant phenotype mirrors features seen in human caudal malformation sy...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003205

    authors: Vlangos CN,Siuniak AN,Robinson D,Chinnaiyan AM,Lyons RH Jr,Cavalcoli JD,Keegan CE

    更新日期:2013-01-01 00:00:00