Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and 53BP1 and functions in the S-phase checkpoint.

Abstract:

:We report on the function of the human ortholog of Saccharomyces cerevisiae Rif1 (Rap1-interacting factor 1). Yeast Rif1 associates with telomeres and regulates their length. In contrast, human Rif1 did not accumulate at functional telomeres, but localized to dysfunctional telomeres and to telomeric DNA clusters in ALT cells, a pattern of telomere association typical of DNA-damage-response factors. After induction of double-strand breaks (DSBs), Rif1 formed foci that colocalized with other DNA-damage-response factors. This response was strictly dependent on ATM (ataxia telangiectasia mutated) and 53BP1, but not affected by diminished function of ATR (ATM- and Rad3-related kinase), BRCA1, Chk2, Nbs1, and Mre11. Rif1 inhibition resulted in radiosensitivity and a defect in the intra-S-phase checkpoint. The S-phase checkpoint phenotype was independent of Nbs1 status, arguing that Rif1 and Nbs1 act in different pathways to inhibit DNA replication after DNA damage. These data reveal that human Rif1 contributes to the ATM-mediated protection against DNA damage and point to a remarkable difference in the primary function of this protein in yeast and mammals.

journal_name

Genes Dev

journal_title

Genes & development

authors

Silverman J,Takai H,Buonomo SB,Eisenhaber F,de Lange T

doi

10.1101/gad.1216004

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

2108-19

issue

17

eissn

0890-9369

issn

1549-5477

pii

18/17/2108

journal_volume

18

pub_type

杂志文章
  • β-Actin mRNA compartmentalization enhances focal adhesion stability and directs cell migration.

    abstract::Directed cell motility is at the basis of biological phenomena such as development, wound healing, and metastasis. It has been shown that substrate attachments mediate motility by coupling the cell's cytoskeleton with force generation. However, it has been unclear how the persistence of cell directionality is facilita...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.190413.112

    authors: Katz ZB,Wells AL,Park HY,Wu B,Shenoy SM,Singer RH

    更新日期:2012-09-01 00:00:00

  • Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.

    abstract::Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a me...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.9.18.2266

    authors: Lydon JP,DeMayo FJ,Funk CR,Mani SK,Hughes AR,Montgomery CA Jr,Shyamala G,Conneely OM,O'Malley BW

    更新日期:1995-09-15 00:00:00

  • Inactivation of AtRac1 by abscisic acid is essential for stomatal closure.

    abstract::Plant water homeostasis is maintained by the phytohormone abscisic acid (ABA), which triggers stomatal pore closure in response to drought stress. We identified the Arabidopsis small guanosine triphosphatase (GTPase) protein AtRac1 as a central component in the ABA-mediated stomatal closure process. ABA treatment indu...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.900401

    authors: Lemichez E,Wu Y,Sanchez JP,Mettouchi A,Mathur J,Chua NH

    更新日期:2001-07-15 00:00:00

  • The incidental pore: CaV1.2 and stem cell activation in quiescent hair follicles.

    abstract::The hair follicle undergoes a lifelong developmental cycle that depends on the integration between activating and inhibitory signals acting to regulate and guide the proliferation and differentiation of pluripotent epithelial stem cells. The effectors and mechanisms responsible for re-entry of quiescent telogen hair f...

    journal_title:Genes & development

    pub_type: 评论,杂志文章

    doi:10.1101/gad.223172.113

    authors: Coulombe PA,Caterina MJ

    更新日期:2013-06-15 00:00:00

  • Dystrophic muscle environment induces changes in cell plasticity.

    abstract::Fibro-adipogenic progenitors (FAPs) reside in the muscle, where they facilitate myofiber regeneration. Under normal conditions, FAPs lack myogenic potential and thus do not directly contribute to regenerated myofibers. Surprisingly, Saccone and colleagues (pp. 841-857) demonstrated that the dystrophic muscle environme...

    journal_title:Genes & development

    pub_type: 评论,杂志文章

    doi:10.1101/gad.241182.114

    authors: Faralli H,Dilworth FJ

    更新日期:2014-04-15 00:00:00

  • The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells.

    abstract::Stem cells do not all respond the same way, but the mechanisms underlying this heterogeneity are not well understood. Here, we found that expression of Hes1 and its downstream genes oscillate in mouse embryonic stem (ES) cells. Those expressing low and high levels of Hes1 tended to differentiate into neural and mesode...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1823109

    authors: Kobayashi T,Mizuno H,Imayoshi I,Furusawa C,Shirahige K,Kageyama R

    更新日期:2009-08-15 00:00:00

  • Genome-wide RNAi analysis of JAK/STAT signaling components in Drosophila.

    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

    authors: Baeg GH,Zhou R,Perrimon N

    更新日期:2005-08-15 00:00:00

  • MT1-MMP regulates the PI3Kδ·Mi-2/NuRD-dependent control of macrophage immune function.

    abstract::Macrophages play critical roles in events ranging from host defense to obesity and cancer, where they infiltrate affected tissues and orchestrate immune responses in tandem with the remodeling of the extracellular matrix (ECM). Despite the dual roles played by macrophages in inflammation, the functions of macrophage-d...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.178749.111

    authors: Shimizu-Hirota R,Xiong W,Baxter BT,Kunkel SL,Maillard I,Chen XW,Sabeh F,Liu R,Li XY,Weiss SJ

    更新日期:2012-02-15 00:00:00

  • Epigenetic effects on yeast transcription caused by mutations in an actin-related protein present in the nucleus.

    abstract::Gene inactivation can result when a delta element of the Ty1 transposon inserted into the yeast HIS4 promoter (his4-912delta) alters the transcription initiation site. Previous work has identified mutations that suppress this transcriptional defect by restoring the transcription start site to the native position, and ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.10.5.604

    authors: Jiang YW,Stillman DJ

    更新日期:1996-03-01 00:00:00

  • Nuclear polyadenylation factors recognize cytoplasmic polyadenylation elements.

    abstract::In the cytoplasm of oocytes and early embryos, addition of poly(A) to mRNAs can activate their translation. We demonstrate that despite many differences between poly(A) addition in the cytoplasm and nucleus, these two forms of polyadenylation may involve identical trans-acting factors. Nuclear polyadenylation requires...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.8.9.1106

    authors: Bilger A,Fox CA,Wahle E,Wickens M

    更新日期:1994-05-01 00:00:00

  • SUMO functions in constitutive transcription and during activation of inducible genes in yeast.

    abstract::Transcription factors represent one of the largest groups of proteins regulated by SUMO (small ubiquitin-like modifier) modification, and their sumoylation is usually associated with transcriptional repression. To investigate whether sumoylation plays a general role in regulating transcription in yeast, we determined ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1917910

    authors: Rosonina E,Duncan SM,Manley JL

    更新日期:2010-06-15 00:00:00

  • Suppressors of a U4 snRNA mutation define a novel U6 snRNP protein with RNA-binding motifs.

    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

    authors: Shannon KW,Guthrie C

    更新日期:1991-05-01 00:00:00

  • A nucleoprotein complex mediates the integration of retroviral DNA.

    abstract::The integration of viral DNA into the host genome is an essential step in the retrovirus life cycle. To understand this process better, we have examined the native state of viral DNA in cells acutely infected by murine leukemia virus (MLV), using both a physical assay for viral DNA and a functional assay for integrati...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.3.4.469

    authors: Bowerman B,Brown PO,Bishop JM,Varmus HE

    更新日期:1989-04-01 00:00:00

  • The mouse homolog of Drosophila Vasa is required for the development of male germ cells.

    abstract::Restricted expression of a mouse Vasa homolog gene (Mvh) expression is first detected in primordial germ cells (PGCs) after colonization of the genital ridges. Subsequently, Mvh is maintained until postmeiotic germ cells are formed. Here, we demonstrate that male mice homozygous for a targeted mutation of Mvh exhibit ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:

    authors: Tanaka SS,Toyooka Y,Akasu R,Katoh-Fukui Y,Nakahara Y,Suzuki R,Yokoyama M,Noce T

    更新日期:2000-04-01 00:00:00

  • Upstream and downstream of mTOR.

    abstract::The evolutionarily conserved checkpoint protein kinase, TOR (target of rapamycin), has emerged as a major effector of cell growth and proliferation via the regulation of protein synthesis. Work in the last decade clearly demonstrates that TOR controls protein synthesis through a stunning number of downstream targets. ...

    journal_title:Genes & development

    pub_type: 杂志文章,评审

    doi:10.1101/gad.1212704

    authors: Hay N,Sonenberg N

    更新日期:2004-08-15 00:00:00

  • Genome-wide analyses identify transcription factors required for proper morphogenesis of Drosophila sensory neuron dendrites.

    abstract::Dendrite arborization patterns are critical determinants of neuronal function. To explore the basis of transcriptional regulation in dendrite pattern formation, we used RNA interference (RNAi) to screen 730 transcriptional regulators and identified 78 genes involved in patterning the stereotyped dendritic arbors of cl...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1391006

    authors: Parrish JZ,Kim MD,Jan LY,Jan YN

    更新日期:2006-04-01 00:00:00

  • Patterns of gene action in plant development revealed by enhancer trap and gene trap transposable elements.

    abstract::The crucifer Arabidopsis thaliana has been used widely as a model organism for the study of plant development. We describe here the development of an efficient insertional mutagenesis system in Arabidopsis that permits identification of genes by their patterns of expression during development. Transposable elements of...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.9.14.1797

    authors: Sundaresan V,Springer P,Volpe T,Haward S,Jones JD,Dean C,Ma H,Martienssen R

    更新日期:1995-07-15 00:00:00

  • UPF1 helicase promotes TSN-mediated miRNA decay.

    abstract::While microRNAs (miRNAs) regulate the vast majority of protein-encoding transcripts, little is known about how miRNAs themselves are degraded. We recently described Tudor-staphylococcal/micrococcal-like nuclease (TSN)-mediated miRNA decay (TumiD) as a cellular pathway in which the nuclease TSN promotes the decay of mi...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.303537.117

    authors: Elbarbary RA,Miyoshi K,Hedaya O,Myers JR,Maquat LE

    更新日期:2017-07-15 00:00:00

  • The cohesin complex and its roles in chromosome biology.

    abstract::Cohesin is a chromosome-associated multisubunit protein complex that is highly conserved in eukaryotes and has close homologs in bacteria. Cohesin mediates cohesion between replicated sister chromatids and is therefore essential for chromosome segregation in dividing cells. Cohesin is also required for efficient repai...

    journal_title:Genes & development

    pub_type: 杂志文章,评审

    doi:10.1101/gad.1724308

    authors: Peters JM,Tedeschi A,Schmitz J

    更新日期:2008-11-15 00:00:00

  • SWI/SNF regulates a transcriptional program that induces senescence to prevent liver cancer.

    abstract::Oncogene-induced senescence (OIS) is a potent tumor suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.286112.116

    authors: Tordella L,Khan S,Hohmeyer A,Banito A,Klotz S,Raguz S,Martin N,Dhamarlingam G,Carroll T,González Meljem JM,Deswal S,Martínez-Barbera JP,García-Escudero R,Zuber J,Zender L,Gil J

    更新日期:2016-10-01 00:00:00

  • H3.3 actively marks enhancers and primes gene transcription via opening higher-ordered chromatin.

    abstract::The histone variants H3.3 and H2A.Z have recently emerged as two of the most important features in transcriptional regulation, the molecular mechanism of which still remains poorly understood. In this study, we investigated the regulation of H3.3 and H2A.Z on chromatin dynamics during transcriptional activation. Our i...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.222174.113

    authors: Chen P,Zhao J,Wang Y,Wang M,Long H,Liang D,Huang L,Wen Z,Li W,Li X,Feng H,Zhao H,Zhu P,Li M,Wang QF,Li G

    更新日期:2013-10-01 00:00:00

  • Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos.

    abstract::Expression of HNF-4, a transcription factor in the steroid hormone receptor superfamily, is detected only in the visceral endoderm of mouse embryos during gastrulation and is expressed in certain embryonic tissues from 8.5 days of gestation. To examine the role of HNF-4 during embryonic development, we disrupted the g...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.8.20.2466

    authors: Chen WS,Manova K,Weinstein DC,Duncan SA,Plump AS,Prezioso VR,Bachvarova RF,Darnell JE Jr

    更新日期:1994-10-15 00:00:00

  • pX, the HBV-encoded coactivator, suppresses the phenotypes of TBP and TAFII250 mutants.

    abstract::Hepatitis B virus (HBV) infects humans and causes a wide range of clinical manifestations, from acute hepatitis to hepatocellular carcinoma (HCC). The HBV genome contains multiple promoters with gene expression regulated predominantly by the cellular transcription initiation machinery. Accordingly, the HBV-encoded pX,...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.12.8.1217

    authors: Haviv I,Matza Y,Shaul Y

    更新日期:1998-04-15 00:00:00

  • Intronic sequence elements impede exon ligation and trigger a discard pathway that yields functional telomerase RNA in fission yeast.

    abstract::The fission yeast telomerase RNA (TER1) precursor harbors an intron immediately downstream from its mature 3' end. Unlike most introns, which are removed from precursor RNAs by the spliceosome in two sequential but tightly coupled transesterification reactions, TER1 only undergoes the first cleavage reaction during te...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.212738.112

    authors: Kannan R,Hartnett S,Voelker RB,Berglund JA,Staley JP,Baumann P

    更新日期:2013-03-15 00:00:00

  • Position effect variegation in Drosophila is associated with an altered chromatin structure.

    abstract::A euchromatic gene placed in the vicinity of heterochromatin by a chromosomal rearrangement generally exhibits position effect variegation (PEV), a clonally inherited pattern showing gene expression in some somatic cells but not in others. The mechanism responsible for this loss of gene expression is investigated here...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.9.10.1263

    authors: Wallrath LL,Elgin SC

    更新日期:1995-05-15 00:00:00

  • Double-bromo and extraterminal (BET) domain proteins regulate dendrite morphology and mechanosensory function.

    abstract::A complex array of genetic factors regulates neuronal dendrite morphology. Epigenetic regulation of gene expression represents a plausible mechanism to control pathways responsible for specific dendritic arbor shapes. By studying the Drosophila dendritic arborization (da) neurons, we discovered a role of the double-br...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.239962.114

    authors: Bagley JA,Yan Z,Zhang W,Wildonger J,Jan LY,Jan YN

    更新日期:2014-09-01 00:00:00

  • Hypersensitivity to DNA damage leads to increased apoptosis during early mouse development.

    abstract::Gastrulation in mice is associated with the start of extreme proliferation and differentiation. The potential cost to the embryo of a very rapid proliferation rate is a high production of damaged cells. We demonstrate a novel surveillance mechanism for the elimination of cells damaged by ionizing radiation during mous...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:

    authors: Heyer BS,MacAuley A,Behrendtsen O,Werb Z

    更新日期:2000-08-15 00:00:00

  • Topoisomerases and yeast rRNA transcription: negative supercoiling stimulates initiation and topoisomerase activity is required for elongation.

    abstract::Previous work has shown that rRNA synthesis is strongly inhibited in yeast top1-top2 double mutants. Here, we show that inactivation of yeast topoisomerases can have paradoxical effects on transcription by RNA polymerase I. For example, transcription of ribosomal minigenes on extrachromosomal plasmids is greatly stimu...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.6.7.1332

    authors: Schultz MC,Brill SJ,Ju Q,Sternglanz R,Reeder RH

    更新日期:1992-07-01 00:00:00

  • Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice.

    abstract::In Saccharomyces cerevisiae, absence of the checkpoint kinase Mec1 (ATR) is viable upon mutations that increase the activity of the ribonucleotide reductase (RNR) complex. Whether this pathway is conserved in mammals remains unknown. Here we show that cells from mice carrying extra alleles of the RNR regulatory subuni...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.256958.114

    authors: Lopez-Contreras AJ,Specks J,Barlow JH,Ambrogio C,Desler C,Vikingsson S,Rodrigo-Perez S,Green H,Rasmussen LJ,Murga M,Nussenzweig A,Fernandez-Capetillo O

    更新日期:2015-04-01 00:00:00

  • Negative feedback maintenance of heme homeostasis by its receptor, Rev-erbalpha.

    abstract::Intracellular heme levels must be tightly regulated to maintain proper mitochondrial respiration while minimizing toxicity, but the homeostatic mechanisms are not well understood. Here we report a novel negative feedback mechanism whereby the nuclear heme receptor Rev-erbalpha tightly controls the level of its own lig...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1825809

    authors: Wu N,Yin L,Hanniman EA,Joshi S,Lazar MA

    更新日期:2009-09-15 00:00:00