Rad54 and DNA Ligase IV cooperate to maintain mammalian chromatid stability.

Abstract:

:Nonhomologous end joining (NHEJ) and homologous recombination (HR) represent the two major pathways of DNA double-strand break (DSB) repair in eukaryotic cells. NHEJ repairs DSBs by ligation of cognate broken ends irrespective of homologous flanking sequences, whereas HR repairs DSBs using an undamaged homologous template. Although both NHEJ and HR have been clearly implicated in the maintenance of genome stability, how these apparently independent and mechanistically distinct pathways are coordinated remains largely unexplored. To investigate the relationship between HR and NHEJ modes of DSB repair, we generated cells doubly deficient for the NHEJ factor DNA Ligase IV (Lig4) and the HR factor Rad54. We show that Lig4 and Rad54 cooperate to support cellular proliferation, repair spontaneous DSBs, and prevent chromosome and single chromatid aberrations. These findings demonstrate a role for NHEJ in the repair of DSBs that occur spontaneously during or after DNA replication, and reveal overlapping functions for NHEJ and Rad54-dependent HR in the repair of such DSBs.

journal_name

Genes Dev

journal_title

Genes & development

authors

Mills KD,Ferguson DO,Essers J,Eckersdorff M,Kanaar R,Alt FW

doi

10.1101/gad.1204304

subject

Has Abstract

pub_date

2004-06-01 00:00:00

pages

1283-92

issue

11

eissn

0890-9369

issn

1549-5477

pii

18/11/1283

journal_volume

18

pub_type

杂志文章
  • Identification of a new APC/C recognition domain, the A box, which is required for the Cdh1-dependent destruction of the kinase Aurora-A during mitotic exit.

    abstract::The mitotic kinase Aurora A (Aur-A) is required for formation of a bipolar mitotic spindle and accurate chromosome segregation. In somatic cells, Aur-A protein and kinase activity levels peak during mitosis, and Aur-A is degraded during mitotic exit. Here, we investigated how Aur-A protein and kinase activity levels a...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1007302

    authors: Littlepage LE,Ruderman JV

    更新日期:2002-09-01 00:00:00

  • Structural insights into Gemin5-guided selection of pre-snRNAs for snRNP assembly.

    abstract::In cytoplasm, the survival of motor neuron (SMN) complex delivers pre-small nuclear RNAs (pre-snRNAs) to the heptameric Sm ring for the assembly of the ring complex on pre-snRNAs at the conserved Sm site [A(U)4-6G]. Gemin5, a WD40 protein component of the SMN complex, is responsible for recognizing pre-snRNAs. In addi...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.288340.116

    authors: Xu C,Ishikawa H,Izumikawa K,Li L,He H,Nobe Y,Yamauchi Y,Shahjee HM,Wu XH,Yu YT,Isobe T,Takahashi N,Min J

    更新日期:2016-11-01 00:00:00

  • The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP1.

    abstract::Apoptosis is an important mechanism to eliminate potentially tumorigenic cells. The tumor suppressor p53 plays a pivotal role in this process. Many tumors harbor mutant p53, but others evade its tumor-suppressive effects by altering the expression of proteins that regulate the p53 pathway. ASPP1 (apoptosis-stimulating...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1954410

    authors: Aylon Y,Ofir-Rosenfeld Y,Yabuta N,Lapi E,Nojima H,Lu X,Oren M

    更新日期:2010-11-01 00:00:00

  • Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state.

    abstract::Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a unique opportunity to derive patient-specific stem cells with potential applications in tissue replacement therapies and without the ethical concerns of human embryonic stem cells (hESCs). However, cellular senescence, which c...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.173922.111

    authors: Lapasset L,Milhavet O,Prieur A,Besnard E,Babled A,Aït-Hamou N,Leschik J,Pellestor F,Ramirez JM,De Vos J,Lehmann S,Lemaitre JM

    更新日期:2011-11-01 00:00:00

  • Regulation of plant innate immunity by three proteins in a complex conserved across the plant and animal kingdoms.

    abstract::Innate immunity against pathogen infection is an evolutionarily conserved process among multicellular organisms. Arabidopsis SNC1 encodes a Resistance protein that combines attributes of multiple mammalian pattern recognition receptors. Utilizing snc1 as an autoimmune model, we identified a discrete protein complex co...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1559607

    authors: Palma K,Zhao Q,Cheng YT,Bi D,Monaghan J,Cheng W,Zhang Y,Li X

    更新日期:2007-06-15 00:00:00

  • Wnt signaling in Xenopus embryos inhibits bmp4 expression and activates neural development.

    abstract::We report a new role for Wnt signaling in the vertebrate embryo: the induction of neural tissue from ectoderm. Early expression of mouse wnt8, Xwnt8, beta-catenin, or dominant-negative GSK3 induces the expression of neural-specific markers and inhibits the expression of Bmp4 in Xenopus ectoderm. We show that Wnt8, but...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.13.23.3149

    authors: Baker JC,Beddington RS,Harland RM

    更新日期:1999-12-01 00:00:00

  • Tango7 directs cellular remodeling by the Drosophila apoptosome.

    abstract::It is now well appreciated that the apoptosome, which governs caspase-dependent cell death, also drives nonapoptotic caspase activation to remodel cells. However, the determinants that specify whether the apoptosome acts to kill or remodel have yet to be identified. Here we report that Tango7 collaborates with the Dro...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.219287.113

    authors: D'Brot A,Chen P,Vaishnav M,Yuan S,Akey CW,Abrams JM

    更新日期:2013-08-01 00:00:00

  • CTD-dependent dismantling of the RNA polymerase II elongation complex by the pre-mRNA 3'-end processing factor, Pcf11.

    abstract::Pcf11 is one of numerous proteins involved in pre-mRNA 3'-end processing and transcription termination. Using elongation complexes (ECs) formed from purified yeast RNA polymerase II (Pol II), we show that a 140-amino acid polypeptide from yeast Pcf11 is capable of dismantling the EC in vitro. This action depends on th...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1296305

    authors: Zhang Z,Fu J,Gilmour DS

    更新日期:2005-07-01 00:00:00

  • Swi/Snf dynamics on stress-responsive genes is governed by competitive bromodomain interactions.

    abstract::The Swi/Snf chromatin remodeling complex functions to alter nucleosome positions by either sliding nucleosomes on DNA or the eviction of histones. The presence of histone acetylation and activator-dependent recruitment and retention of Swi/Snf is important for its efficient function. It is not understood, however, why...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.243584.114

    authors: Dutta A,Gogol M,Kim JH,Smolle M,Venkatesh S,Gilmore J,Florens L,Washburn MP,Workman JL

    更新日期:2014-10-15 00:00:00

  • SCH9, a gene of Saccharomyces cerevisiae that encodes a protein distinct from, but functionally and structurally related to, cAMP-dependent protein kinase catalytic subunits.

    abstract::A new gene, SCH9, was isolated from Saccharomyces cerevisiae by its ability to complement a cdc25ts mutation. Sequence analysis indicates that it encodes a 90,000-dalton protein with a carboxy-terminal domain homologous to yeast and mammalian cAMP-dependent protein kinase catalytic subunits. In addition to suppressing...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.2.5.517

    authors: Toda T,Cameron S,Sass P,Wigler M

    更新日期:1988-05-01 00:00:00

  • BRCA1/BARD1 inhibition of mRNA 3' processing involves targeted degradation of RNA polymerase II.

    abstract::Mammalian cells exhibit a complex response to DNA damage. The tumor suppressor BRCA1 and associated protein BARD1 are thought to play an important role in this response, and our previous work demonstrated that this includes transient inhibition of the pre-mRNA 3' processing machinery. Here we provide evidence that thi...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1309505

    authors: Kleiman FE,Wu-Baer F,Fonseca D,Kaneko S,Baer R,Manley JL

    更新日期:2005-05-15 00:00:00

  • Targeting Argonaute to chromatin.

    abstract::In many eukaryotes, siRNAs bound to Argonaute proteins guide chromatin-modifying enzymes to complementary loci, resulting in transcriptional gene silencing. Multiple lines of evidence indicate that siRNAs base-pair with longer RNAs produced at target loci, but the possibility that siRNAs base-pair directly with DNA re...

    journal_title:Genes & development

    pub_type: 评论,杂志文章

    doi:10.1101/gad.294900.116

    authors: Wendte JM,Pikaard CS

    更新日期:2016-12-15 00:00:00

  • Dual pathways for induction of wingless expression by protein kinase A and Hedgehog in Drosophila embryos.

    abstract::The secreted Drosophila Hedgehog (Hh) protein induces transcription of specific genes by an unknown mechanism that requires the serpentine transmembrane protein Smoothened (Smo) and the transcription factor Cubitus interruptus (Ci). Protein kinase A (PKA) has been implicated in the mechanism of Hh signal transduction ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.11.17.2250

    authors: Ohlmeyer JT,Kalderon D

    更新日期:1997-09-01 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

  • The neuron-specific RNA-binding protein ELAV regulates neuroglian alternative splicing in neurons and binds directly to its pre-mRNA.

    abstract::Drosophila melanogaster neural-specific protein, ELAV, has been shown to regulate the neural-specific splicing of three genes: neuroglian (nrg), erect wing, and armadillo. Alternative splicing of the nrg transcript involves alternative inclusion of a 3'-terminal exon. Here, using a minigene reporter, we show that the ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.903101

    authors: Lisbin MJ,Qiu J,White K

    更新日期:2001-10-01 00:00:00

  • Tandem AP-1-binding sites within the human beta-globin dominant control region function as an inducible enhancer in erythroid cells.

    abstract::A powerful enhancer has been mapped to an 18-bp DNA segment located 11 kb 5' to the human epsilon-globin gene within the dominant control or locus-activating region. This enhancer is inducible in K562 human erythroleukemia cells, increasing linked gamma-globin promoter/luciferase gene expression to 170-fold over an en...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.4.6.993

    authors: Ney PA,Sorrentino BP,McDonagh KT,Nienhuis AW

    更新日期:1990-06-01 00:00:00

  • sel-10, a negative regulator of lin-12 activity in Caenorhabditis elegans, encodes a member of the CDC4 family of proteins.

    abstract::Mutations that influence lin-12 activity in Caenorhabditis elegans may identify conserved factors that regulate the activity of lin-12/Notch proteins. We describe genetic evidence indicating that sel-10 is a negative regulator of lin-12/Notch-mediated signaling in C. elegans. Sequence analysis shows that SEL-10 is a m...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.11.23.3182

    authors: Hubbard EJ,Wu G,Kitajewski J,Greenwald I

    更新日期:1997-12-01 00:00:00

  • Reconstitution of human TFIIA activity from recombinant polypeptides: a role in TFIID-mediated transcription.

    abstract::Human TFIIA activity is composed of three subunits (alpha, beta, gamma). Here we report the isolation of a human cDNA clone encoding the gamma-subunit and the reconstitution of TFIIA activity from recombinant polypeptides (holo-TFIIA). Protein-protein interaction analysis established that the beta and gamma subunits o...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.8.19.2336

    authors: Sun X,Ma D,Sheldon M,Yeung K,Reinberg D

    更新日期:1994-10-01 00:00:00

  • The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for smad3 in TGF-beta-induced transcriptional activation.

    abstract::Smads regulate transcription of defined genes in response to TGF-beta receptor activation, although the mechanisms of Smad-mediated transcription are not well understood. We demonstrate that the TGF-beta-inducible Smad3 uses the tumor suppressor Smad4/DPC4 and CBP/p300 as transcriptional coactivators, which associate ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.12.14.2153

    authors: Feng XH,Zhang Y,Wu RY,Derynck R

    更新日期:1998-07-15 00:00:00

  • Alternative splicing of the sex determination gene transformer-2 is sex-specific in the germ line but not in the soma.

    abstract::The transformer-2 (tra-2) gene of Drosophila melanogaster plays essential roles in both sexual differentiation in the female soma and spermatogenesis in the male germ line. In the female soma, tra-2 is known to act with other genes in the sex determination regulatory cascade to control the sex-specific alternative spl...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.4.5.789

    authors: Mattox W,Palmer MJ,Baker BS

    更新日期:1990-05-01 00:00:00

  • Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes.

    abstract::The Komeda miniature rat Ishikawa (KMI) is a naturally occurring mutant caused by an autosomal recessive mutation mri, which exhibits longitudinal growth retardation. Here we identified the mri mutation as a deletion in the rat gene encoding cGMP-dependent protein kinase type II (cGKII). KMIs showed an expanded growth...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1224204

    authors: Chikuda H,Kugimiya F,Hoshi K,Ikeda T,Ogasawara T,Shimoaka T,Kawano H,Kamekura S,Tsuchida A,Yokoi N,Nakamura K,Komeda K,Chung UI,Kawaguchi H

    更新日期:2004-10-01 00:00:00

  • Smad3-dependent nuclear translocation of beta-catenin is required for TGF-beta1-induced proliferation of bone marrow-derived adult human mesenchymal stem cells.

    abstract::Adult mesenchymal stem cells (MSCs) derived from bone marrow contribute to the regeneration of multiple types of mesenchymal tissues. Here we describe the functional role of a novel form of cross-talk between the transforming growth factor beta1 (TGF-beta1) and Wnt signaling pathways in regulating the activities of hu...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1388806

    authors: Jian H,Shen X,Liu I,Semenov M,He X,Wang XF

    更新日期:2006-03-15 00:00:00

  • Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis.

    abstract::DNA methylation is tightly regulated throughout mammalian development, and altered DNA methylation patterns are a general hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in hematological disorders, including acute myeloid leukemia (AML), and has been suggested to protect CG dinucleotide (...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.260174.115

    authors: Rasmussen KD,Jia G,Johansen JV,Pedersen MT,Rapin N,Bagger FO,Porse BT,Bernard OA,Christensen J,Helin K

    更新日期:2015-05-01 00:00:00

  • Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B.

    abstract::Covalent modifications of the histone N tails play important roles in eukaryotic gene expression. Histone acetylation, in particular, is required for the activation of a subset of eukaryotic genes through the targeted recruitment of histone acetyltransferases. We have reported that a histone C tail modification, ubiqu...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1149604

    authors: Kao CF,Hillyer C,Tsukuda T,Henry K,Berger S,Osley MA

    更新日期:2004-01-15 00:00:00

  • Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants.

    abstract::The Notch signaling pathway is essential for embryonic vascular development in vertebrates. Here we show that mouse embryos heterozygous for a targeted mutation in the gene encoding the DLL4 ligand exhibit haploinsufficient lethality because of defects in vascular remodeling. We also describe vascular defects in embry...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1239204

    authors: Krebs LT,Shutter JR,Tanigaki K,Honjo T,Stark KL,Gridley T

    更新日期:2004-10-15 00:00:00

  • The RNA helicase MOV10L1 binds piRNA precursors to initiate piRNA processing.

    abstract::Piwi-piRNA (Piwi-interacting RNA) ribonucleoproteins (piRNPs) enforce retrotransposon silencing, a function critical for preserving the genome integrity of germ cells. The molecular functions of most of the factors that have been genetically implicated in primary piRNA biogenesis are still elusive. Here we show that M...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.254631.114

    authors: Vourekas A,Zheng K,Fu Q,Maragkakis M,Alexiou P,Ma J,Pillai RS,Mourelatos Z,Wang PJ

    更新日期:2015-03-15 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

  • The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment.

    abstract::Post-translational modifications of conserved N-terminal tail residues in histones regulate many aspects of chromosome activity. Thr 3 of histone H3 is highly conserved, but the significance of its phosphorylation is unclear, and the identity of the corresponding kinase unknown. Immunostaining with phospho-specific an...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1267105

    authors: Dai J,Sultan S,Taylor SS,Higgins JM

    更新日期:2005-02-15 00:00:00

  • The Caenorhabditis elegans SOMI-1 zinc finger protein and SWI/SNF promote regulation of development by the mir-84 microRNA.

    abstract::Hundreds of microRNAs (miRNAs) have been discovered in metazoans and plants, and understanding of their biogenesis has advanced dramatically; however, relatively little is known about the cofactors necessary for miRNA regulation of target gene expression. In Caenorhabditis elegans, the conserved miRNA let-7 and its pa...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.17153811

    authors: Hayes GD,Riedel CG,Ruvkun G

    更新日期:2011-10-01 00:00:00

  • Nuclear myosin I acts in concert with polymeric actin to drive RNA polymerase I transcription.

    abstract::Actin is associated with all three nuclear RNA polymerases and acts in concert with nuclear myosin I (NM1) to drive transcription. Practically nothing is known regarding the state of actin and the functional interplay of actin and NM1 in transcription. Here we show that actin and NM1 act in concert to promote RNA poly...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.455908

    authors: Ye J,Zhao J,Hoffmann-Rohrer U,Grummt I

    更新日期:2008-02-01 00:00:00