RNase H eliminates R-loops that disrupt DNA replication but is nonessential for efficient DSB repair.

Abstract:

:In Saccharomyces cerevisiae, genome stability depends on RNases H1 and H2, which remove ribonucleotides from DNA and eliminate RNA-DNA hybrids (R-loops). In Schizosaccharomyces pombe, RNase H enzymes were reported to process RNA-DNA hybrids produced at a double-strand break (DSB) generated by I-PpoI meganuclease. However, it is unclear if RNase H is generally required for efficient DSB repair in fission yeast, or whether it has other genome protection roles. Here, we show that S. pombe rnh1∆ rnh201∆ cells, which lack the RNase H enzymes, accumulate R-loops and activate DNA damage checkpoints. Their viability requires critical DSB repair proteins and Mus81, which resolves DNA junctions formed during repair of broken replication forks. "Dirty" DSBs generated by ionizing radiation, as well as a "clean" DSB at a broken replication fork, are efficiently repaired in the absence of RNase H. RNA-DNA hybrids are not detected at a reparable DSB formed by fork collapse. We conclude that unprocessed R-loops collapse replication forks in rnh1∆ rnh201∆ cells, but RNase H is not generally required for efficient DSB repair.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Zhao H,Zhu M,Limbo O,Russell P

doi

10.15252/embr.201745335

subject

Has Abstract

pub_date

2018-05-01 00:00:00

issue

5

eissn

1469-221X

issn

1469-3178

pii

embr.201745335

journal_volume

19

pub_type

杂志文章
  • R3hdml regulates satellite cell proliferation and differentiation.

    abstract::In this study, we identified a previously uncharacterized skeletal satellite cell-secreted protein, R3h domain containing-like (R3hdml). Expression of R3hdml increases during skeletal muscle development and differentiation in mice. Body weight and skeletal muscle mass of R3hdml knockout (KO) mice are lower compared to...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201947957

    authors: Sakamoto K,Furuichi Y,Yamamoto M,Takahashi M,Akimoto Y,Ishikawa T,Shimizu T,Fujimoto M,Takada-Watanabe A,Hayashi A,Mita Y,Manabe Y,Fujii NL,Ishibashi R,Maezawa Y,Betsholtz C,Yokote K,Takemoto M

    更新日期:2019-11-05 00:00:00

  • Small-molecule inhibition of aging-associated chromosomal instability delays cellular senescence.

    abstract::Chromosomal instability (CIN) refers to the rate at which cells are unable to properly segregate whole chromosomes, leading to aneuploidy. Besides its prevalence in cancer cells and postulated implications in promoting tumorigenesis, studies in aneuploidy-prone mouse models uncovered an unanticipated link between CIN ...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201949248

    authors: Barroso-Vilares M,Macedo JC,Reis M,Warren JD,Compton D,Logarinho E

    更新日期:2020-05-06 00:00:00

  • Progressive dosage compensation during Drosophila embryogenesis is reflected by gene arrangement.

    abstract::In Drosophila melanogaster males, X-chromosome monosomy is compensated by chromosome-wide transcription activation. We found that complete dosage compensation during embryogenesis takes surprisingly long and is incomplete even after 10 h of development. Although the activating dosage compensation complex (DCC) associa...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201948138

    authors: Prayitno K,Schauer T,Regnard C,Becker PB

    更新日期:2019-08-01 00:00:00

  • Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex.

    abstract::Histone deacetylases (HDACs)-an enzyme family that deacetylates histones and non-histone proteins-are implicated in human diseases such as cancer, and the first-generation of HDAC inhibitors are now in clinical trials. Here, we report the 2.0 A resolution crystal structure of a catalytically inactive HDAC8 active-site...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.7401047

    authors: Vannini A,Volpari C,Gallinari P,Jones P,Mattu M,Carfí A,De Francesco R,Steinkühler C,Di Marco S

    更新日期:2007-09-01 00:00:00

  • Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest.

    abstract::Individuals affected by the autosomal recessive disorder Werner's syndrome (WS) develop many of the symptoms characteristic of premature ageing. Primary fibroblasts cultured from WS patients exhibit karyotypic abnormalities and a reduced replicative life span. The WRN gene encodes a 3'-5' DNA helicase, and is a member...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kvd004

    authors: Constantinou A,Tarsounas M,Karow JK,Brosh RM,Bohr VA,Hickson ID,West SC

    更新日期:2000-07-01 00:00:00

  • The wild-type Schizosaccharomyces pombe mat1 imprint consists of two ribonucleotides.

    abstract::The imprint at the mat1 locus of Schizosaccharomyces pombe acts to initiate the replication-coupled recombination event that underlies mating-type switching. However, the nature of the imprint has been an area of dispute. Two alternative models have been proposed: one stated that the imprint is a nick in the DNA, wher...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.7400576

    authors: Vengrova S,Dalgaard JZ

    更新日期:2006-01-01 00:00:00

  • Quantitative analysis of snoRNA association with pre-ribosomes and release of snR30 by Rok1 helicase.

    abstract::In yeast, three small nucleolar RNAs (snoRNAs) are essential for the processing of pre-ribosomal RNA--U3, U14 and snR30--whereas 72 non-essential snoRNAs direct site-specific modification of pre-rRNA. We applied a quantitative screen for alterations in the pre-ribosome association to all 75 yeast snoRNAs in strains de...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/embor.2008.184

    authors: Bohnsack MT,Kos M,Tollervey D

    更新日期:2008-12-01 00:00:00

  • Replication-independent chromatin loading of Dnmt1 during G2 and M phases.

    abstract::The major DNA methyltransferase, Dnmt1, associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand. In view of the slow kinetics of Dnmt1 in vitro versus the fast progression of the replication fork, we have tested whether Dnmt1 associates with chromatin beyond...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.7400295

    authors: Easwaran HP,Schermelleh L,Leonhardt H,Cardoso MC

    更新日期:2004-12-01 00:00:00

  • Phosphorylation of ubiquitin at Ser65 affects its polymerization, targets, and proteome-wide turnover.

    abstract::Ubiquitylation is an essential post-translational modification that regulates numerous cellular processes, most notably protein degradation. Ubiquitin can itself be phosphorylated at nearly every serine, threonine, and tyrosine residue. However, the effect of this modification on ubiquitin function is largely unknown....

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201540298

    authors: Swaney DL,Rodríguez-Mias RA,Villén J

    更新日期:2015-09-01 00:00:00

  • The 18S ribosomal RNA m6 A methyltransferase Mettl5 is required for normal walking behavior in Drosophila.

    abstract::RNA modifications have recently emerged as an important layer of gene regulation. N6-methyladenosine (m6 A) is the most prominent modification on eukaryotic messenger RNA and has also been found on noncoding RNA, including ribosomal and small nuclear RNA. Recently, several m6 A methyltransferases were identified, unco...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201949443

    authors: Leismann J,Spagnuolo M,Pradhan M,Wacheul L,Vu MA,Musheev M,Mier P,Andrade-Navarro MA,Graille M,Niehrs C,Lafontaine DL,Roignant JY

    更新日期:2020-07-03 00:00:00

  • Redox activation of ATM enhances GSNOR translation to sustain mitophagy and tolerance to oxidative stress.

    abstract::The denitrosylase S-nitrosoglutathione reductase (GSNOR) has been suggested to sustain mitochondrial removal by autophagy (mitophagy), functionally linking S-nitrosylation to cell senescence and aging. In this study, we provide evidence that GSNOR is induced at the translational level in response to hydrogen peroxide ...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.202050500

    authors: Cirotti C,Rizza S,Giglio P,Poerio N,Allega MF,Claps G,Pecorari C,Lee JH,Benassi B,Barilà D,Robert C,Stamler JS,Cecconi F,Fraziano M,Paull TT,Filomeni G

    更新日期:2020-11-27 00:00:00

  • Distinct roles for β-arrestin2 and arrestin-domain-containing proteins in β2 adrenergic receptor trafficking.

    abstract::β-arrestin 1 and 2 (also known as arrestin 2 and 3) are homologous adaptor proteins that regulate seven-transmembrane receptor trafficking and signalling. Other proteins with predicted 'arrestin-like' structural domains but lacking sequence homology have been indicated to function like β-arrestin in receptor regulatio...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/embor.2012.187

    authors: Han SO,Kommaddi RP,Shenoy SK

    更新日期:2013-02-01 00:00:00

  • Do scientists read enough fiction?

    abstract::Reading the academic literature is an essential part of a scientist's job. David Smith argues that reading fiction can be even more important for creativity and productivity than papers and reviews. ...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.202052206

    authors: Smith DR

    更新日期:2021-01-04 00:00:00

  • Transfer of extracellular vesicle-microRNA controls germinal center reaction and antibody production.

    abstract::Intercellular communication orchestrates effective immune responses against disease-causing agents. Extracellular vesicles (EVs) are potent mediators of cell-cell communication. EVs carry bioactive molecules, including microRNAs, which modulate gene expression and function in the recipient cell. Here, we show that for...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201948925

    authors: Fernández-Messina L,Rodríguez-Galán A,de Yébenes VG,Gutiérrez-Vázquez C,Tenreiro S,Seabra MC,Ramiro AR,Sánchez-Madrid F

    更新日期:2020-04-03 00:00:00

  • Dynactin-membrane interaction is regulated by the C-terminal domains of p150(Glued).

    abstract::Dynactin has been proposed to link the microtubule-associated motor cytoplasmic dynein with membranous cargo; however, the mechanism by which dynactin-membrane interaction is regulated is unknown. Here we show that dynein and dynactin exist in discrete cytosolic and membrane-bound states in the filamentous fungus Neur...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kve202

    authors: Kumar S,Zhou Y,Plamann M

    更新日期:2001-10-01 00:00:00

  • Comment on "Close loop peer review" by Michael Hill.

    abstract::Comment on "Close loop peer review" by Michael Hill. ...

    journal_title:EMBO reports

    pub_type: 评论,信件

    doi:10.15252/embr.201948313

    authors: Horowitz A

    更新日期:2019-08-01 00:00:00

  • The Gam protein of bacteriophage Mu is an orthologue of eukaryotic Ku.

    abstract::Mu bacteriophage inserts its DNA into the genome of host bacteria and is used as a model for DNA transposition events in other systems. The eukaryotic Ku protein has key roles in DNA repair and in certain transposition events. Here we show that the Gam protein of phage Mu is conserved in bacteria, has sequence homolog...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.embor709

    authors: d'Adda di Fagagna F,Weller GR,Doherty AJ,Jackson SP

    更新日期:2003-01-01 00:00:00

  • Loss of genomic integrity induced by lysosphingolipid imbalance drives ageing in the heart.

    abstract::Cardiac dysfunctions dramatically increase with age. Revealing a currently unknown contributor to cardiac ageing, we report the age-dependent, cardiac-specific accumulation of the lysosphingolipid sphinganine (dihydrosphingosine, DHS) as an evolutionarily conserved hallmark of the aged vertebrate heart. Mechanisticall...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201847407

    authors: Ahuja G,Bartsch D,Yao W,Geissen S,Frank S,Aguirre A,Russ N,Messling JE,Dodzian J,Lagerborg KA,Vargas NE,Muck JS,Brodesser S,Baldus S,Sachinidis A,Hescheler J,Dieterich C,Trifunovic A,Papantonis A,Petrascheck M,Kli

    更新日期:2019-04-01 00:00:00

  • LGR5 controls extracellular matrix production by stem cells in the developing intestine.

    abstract::The Lgr5 receptor is a marker of intestinal stem cells (ISCs) that regulates Wnt/b-catenin signaling. In this study, phenotype analysis of knockin/knockout Lgr5-eGFP-IRES-Cre and Lgr5-DTReGFP embryos reveals that Lgr5 deficiency during Wnt-mediated cytodifferentiation results in amplification of ISCs and early differe...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201949224

    authors: Fernandez Vallone V,Leprovots M,Ribatallada-Soriano D,Gerbier R,Lefort A,Libert F,Vassart G,Garcia MI

    更新日期:2020-07-03 00:00:00

  • ARGONAUTE 1 homeostasis invokes the coordinate action of the microRNA and siRNA pathways.

    abstract::ARGONAUTE 1 (AGO1) slices endogenous messenger RNAs (mRNAs) during both microRNA (miRNA)- and short interfering RNA (siRNA)-guided post-transcriptional silencing. We have previously reported that AGO1 homeostasis is maintained through the repressive action of miR168 on AGO1 mRNA and the stabilizing effect of AGO1 prot...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/embor.2009.32

    authors: Mallory AC,Vaucheret H

    更新日期:2009-05-01 00:00:00

  • Epigenome changes in active and inactive polycomb-group-controlled regions.

    abstract::The Polycomb group (PcG) of proteins conveys epigenetic inheritance of repressed transcriptional states. In Drosophila, the Polycomb repressive complex 1 (PRC1) maintains the silent state by inhibiting the transcription machinery and chromatin remodelling at core promoters. Using immunoprecipitation of in vivo formald...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.7400260

    authors: Breiling A,O'Neill LP,D'Eliseo D,Turner BM,Orlando V

    更新日期:2004-10-01 00:00:00

  • Chromosome misalignments induce spindle-positioning defects.

    abstract::Cortical pulling forces on astral microtubules are essential to position the spindle. These forces are generated by cortical dynein, a minus-end directed motor. Previously, another dynein regulator termed Spindly was proposed to regulate dynein-dependent spindle positioning. However, the mechanism of how Spindly regul...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201541143

    authors: Tame MA,Raaijmakers JA,Afanasyev P,Medema RH

    更新日期:2016-03-01 00:00:00

  • Map7/7D1 and Dvl form a feedback loop that facilitates microtubule remodeling and Wnt5a signaling.

    abstract::The Wnt signaling pathway can be grouped into two classes, the β-catenin-dependent and β-catenin-independent pathways. Wnt5a signaling through a β-catenin-independent pathway promotes microtubule (MT) remodeling during cell-substrate adhesion, cell migration, and planar cell polarity formation. Although Wnt5a signalin...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201745471

    authors: Kikuchi K,Nakamura A,Arata M,Shi D,Nakagawa M,Tanaka T,Uemura T,Fujimori T,Kikuchi A,Uezu A,Sakamoto Y,Nakanishi H

    更新日期:2018-07-01 00:00:00

  • Senescence and apoptosis: dueling or complementary cell fates?

    abstract::In response to a variety of stresses, mammalian cells undergo a persistent proliferative arrest known as cellular senescence. Many senescence-inducing stressors are potentially oncogenic, strengthening the notion that senescence evolved alongside apoptosis to suppress tumorigenesis. In contrast to apoptosis, senescent...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审

    doi:10.15252/embr.201439245

    authors: Childs BG,Baker DJ,Kirkland JL,Campisi J,van Deursen JM

    更新日期:2014-11-01 00:00:00

  • Crucial structural role for the PH and C1 domains of the Vav1 exchange factor.

    abstract::The Vav family of proteins are guanine nucleotide exchange factors (GEFs) for the Rho family of GTPases, which regulate various cellular functions, including T-cell activation. They contain a catalytic Dbl homology (DH) domain that is invariably followed by a pleckstrin homology (PH) domain, which is often required fo...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/embor.2008.80

    authors: Rapley J,Tybulewicz VL,Rittinger K

    更新日期:2008-07-01 00:00:00

  • Introns and their positions affect the translational activity of mRNA in plant cells.

    abstract::In an attempt to further increase transgene expression levels in plants over and above the enhancement obtained with a 5' untranslated leader intron, three different maize introns were inserted at three different positions within the coding sequence of the luciferase reporter gene. Constructs were transformed into mai...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1093/embo-reports/kve090

    authors: Bourdon V,Harvey A,Lonsdale DM

    更新日期:2001-05-01 00:00:00

  • Switching of chromatin-remodelling complexes for oestrogen receptor-alpha.

    abstract::The female sex steroid hormone oestrogen stimulates both cell proliferation and cell differentiation in target tissues. These biological actions are mediated primarily through nuclear oestrogen receptors (ERs). The ligand-dependent transactivation of ERs requires several nuclear co-regulator complexes; however, the ce...

    journal_title:EMBO reports

    pub_type: 杂志文章,收录出版

    doi:10.1038/embor.2008.55

    authors: Okada M,Takezawa S,Mezaki Y,Yamaoka I,Takada I,Kitagawa H,Kato S

    更新日期:2008-06-01 00:00:00

  • Regulation of TOR by small GTPases.

    abstract::TOR is a conserved serine/threonine kinase that responds to nutrients, growth factors, the bioenergetic status of the cell and cellular stress to control growth, metabolism and ageing. A diverse group of small GTPases including Rheb, Rag, Rac1, RalA and Ryh1 play a variety of roles in the regulation of TOR. For exampl...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审

    doi:10.1038/embor.2011.257

    authors: Durán RV,Hall MN

    更新日期:2012-02-01 00:00:00

  • Zika virus depletes neural stem cells and evades selective autophagy by suppressing the Fanconi anemia protein FANCC.

    abstract::Zika virus (ZIKV) is an emerging flavivirus, which when passed through vertical transmission from mother to developing fetus can lead to developmental abnormalities, including microcephaly. While there is mounting evidence that suggests a causal relationship between ZIKV infection and microcephaly, the mechanisms by w...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.15252/embr.201949183

    authors: Tiwari SK,Dang JW,Lin N,Qin Y,Wang S,Rana TM

    更新日期:2020-10-19 00:00:00

  • Crystal structure of Mil (Mth680): internal duplication and similarity between the Imp4/Brix domain and the anticodon-binding domain of class IIa aminoacyl-tRNA synthetases.

    abstract::Proteins of the Imp4/Brix superfamily are involved in ribosomal RNA processing, an essential function in all cells. We report the first structure of an Imp4/Brix superfamily protein, the Mil (for Methanothermobacter thermautotrophicus Imp4-like) protein (gene product Mth680), from the archaeon M. thermautotrophicus. T...

    journal_title:EMBO reports

    pub_type: 杂志文章

    doi:10.1038/sj.embor.7400328

    authors: Ng CL,Waterman D,Koonin EV,Antson AA,Ortiz-Lombardía M

    更新日期:2005-02-01 00:00:00