Genome integrity and disease prevention in the nervous system.

Abstract:

:Multiple DNA repair pathways maintain genome stability and ensure that DNA remains essentially unchanged over the life of a cell. Various human diseases occur if DNA repair is compromised, and most of these impact the nervous system, in some cases exclusively. However, it is often unclear what specific endogenous damage underpins disease pathology. Generally, the types of causative DNA damage are associated with replication, transcription, or oxidative metabolism; other direct sources of endogenous lesions may arise from aberrant topoisomerase activity or ribonucleotide incorporation into DNA. This review focuses on the etiology of DNA damage in the nervous system and the genome stability pathways that prevent human neurologic disease.

journal_name

Genes Dev

journal_title

Genes & development

authors

McKinnon PJ

doi

10.1101/gad.301325.117

subject

Has Abstract

pub_date

2017-06-15 00:00:00

pages

1180-1194

issue

12

eissn

0890-9369

issn

1549-5477

pii

31/12/1180

journal_volume

31

pub_type

杂志文章,评审
  • Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors.

    abstract::Multiple congenital disorders often present complex phenotypes, but how the mutation of individual genetic factors can lead to multiple defects remains poorly understood. In the present study, we used human neuroepithelial (NE) cells and CHARGE patient-derived cells as an in vitro model system to identify the function...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.301887.117

    authors: Chai M,Sanosaka T,Okuno H,Zhou Z,Koya I,Banno S,Andoh-Noda T,Tabata Y,Shimamura R,Hayashi T,Ebisawa M,Sasagawa Y,Nikaido I,Okano H,Kohyama J

    更新日期:2018-01-15 00:00:00

  • Characterization of a murine homeo box gene, Hox-2.6, related to the Drosophila Deformed gene.

    abstract::The Hox-2 locus on chromosome 11 represents one of the major clusters of homeo-box-containing genes in the mouse. We have identified two new members (Hox-2.6 and Hox-2.7), which form part of this cluster of seven linked genes, and it appears that the Hox-2 locus is related by duplication and divergence to at least one...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.2.11.1424

    authors: Graham A,Papalopulu N,Lorimer J,McVey JH,Tuddenham EG,Krumlauf R

    更新日期:1988-11-01 00:00:00

  • In vivo target of a transcriptional activator revealed by fluorescence resonance energy transfer.

    abstract::Our understanding of eukaryotic transcriptional activation mechanisms has been hampered by an inability to identify the direct in vivo targets of activator proteins, primarily because of lack of appropriate experimental methods. To circumvent this problem, we have developed a fluorescence resonance energy transfer (FR...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1148404

    authors: Bhaumik SR,Raha T,Aiello DP,Green MR

    更新日期:2004-02-01 00:00:00

  • A six-amino-acid motif is a major determinant in functional evolution of HOX1 proteins.

    abstract::Gene duplication and divergence is a major driver in the emergence of evolutionary novelties. How variations in amino acid sequences lead to loss of ancestral activity and functional diversification of proteins is poorly understood. We used cross-species functional analysis of Drosophila Labial and its mouse HOX1 orth...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.342329.120

    authors: Singh NP,De Kumar B,Paulson A,Parrish ME,Zhang Y,Florens L,Conaway JW,Si K,Krumlauf R

    更新日期:2020-12-01 00:00:00

  • Not just scaffolding: plectin regulates actin dynamics in cultured cells.

    abstract::Plectin, a major linker and scaffolding protein of the cytoskeleton, has been shown to be essential for the mechanical integrity of skin, skeletal muscle, and heart. Studying fibroblast and astroglial cell cultures derived from plectin (-/-) mice, we found that their actin cytoskeleton, including focal adhesion contac...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.12.21.3442

    authors: Andrä K,Nikolic B,Stöcher M,Drenckhahn D,Wiche G

    更新日期:1998-11-01 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

  • On the role of homologous sequences in chromosomal rearrangements.

    abstract::Deletions and other chromosomal rearrangements can be generated by recombination between repeated sequences. It has been shown in a number of systems that the probability of exchange or gene conversion decreases with increasing distance between repeats. This paper examines the question of how repeats find each other, ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.2.12b.1800

    authors: Singer BS

    更新日期:1988-12-01 00:00:00

  • Physical and functional interactions between polo kinase and the spindle pole component Cut12 regulate mitotic commitment in S. pombe.

    abstract::Commitment to mitosis is regulated by a protein kinase complex called MPF. MPF is inhibited by Wee1-related kinases and activated by Cdc25 phosphatase. MPF activation further boosts Cdc25 and represses Wee1. This feedback control probably involves polo kinase. A dominant cut12.s11 mutation in the Schizosaccharomyces p...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.256003

    authors: MacIver FH,Tanaka K,Robertson AM,Hagan IM

    更新日期:2003-06-15 00:00:00

  • DOT1L regulates dystrophin expression and is critical for cardiac function.

    abstract::Histone methylation plays an important role in regulating gene expression. One such methylation occurs at Lys 79 of histone H3 (H3K79) and is catalyzed by the yeast DOT1 (disruptor of telomeric silencing) and its mammalian homolog, DOT1L. Previous studies have demonstrated that germline disruption of Dot1L in mice res...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.2018511

    authors: Nguyen AT,Xiao B,Neppl RL,Kallin EM,Li J,Chen T,Wang DZ,Xiao X,Zhang Y

    更新日期:2011-02-01 00:00:00

  • RNAi drives nonreciprocal translocations at eroding chromosome ends to establish telomere-free linear chromosomes.

    abstract::The identification of telomerase-negative HAATI (heterochromatin amplification-mediated and telomerase-independent) cells, in which telomeres are superseded by nontelomeric heterochromatin tracts, challenged the idea that canonical telomeres are essential for chromosome linearity and raised crucial questions as to how...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.311712.118

    authors: Begnis M,Apte MS,Masuda H,Jain D,Wheeler DL,Cooper JP

    更新日期:2018-04-01 00:00:00

  • Homeless is required for RNA localization in Drosophila oogenesis and encodes a new member of the DE-H family of RNA-dependent ATPases.

    abstract::The homeless (hls) gene of Drosophila is required for anteroposterior and dorsoventral axis formation during oogenesis. At a low frequency, females homozygous for mutations in hls generate early egg chambers in which the oocyte is positioned incorrectly within the cyst. At a high frequency, late-stage egg chambers exh...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.9.20.2495

    authors: Gillespie DE,Berg CA

    更新日期:1995-10-15 00:00:00

  • Identification of cis-acting sites for condensin loading onto budding yeast chromosomes.

    abstract::Eukaryotic chromosomes reach their stable rod-shaped appearance in mitosis in a reaction dependent on the evolutionarily conserved condensin complex. Little is known about how and where condensin associates with chromosomes. Here, we analyze condensin binding to budding yeast chromosomes using high-resolution oligonuc...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1675708

    authors: D'Ambrosio C,Schmidt CK,Katou Y,Kelly G,Itoh T,Shirahige K,Uhlmann F

    更新日期:2008-08-15 00:00:00

  • Factors (TAFs) required for activated transcription interact with TATA box-binding protein conserved core domain.

    abstract::TFIID is a multisubunit protein containing the TATA box-binding polypeptide (TBP) and associated factors (TFIID-TAFs) required for activated transcription by RNA polymerase II. TBPs from different eukaryotes contain a highly conserved carboxy-terminal domain and very divergent amino-terminal domains. Earlier studies p...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.7.2.180

    authors: Zhou Q,Boyer TG,Berk AJ

    更新日期:1993-02-01 00:00:00

  • GCN5 is a required cofactor for a ubiquitin ligase that targets NF-kappaB/RelA.

    abstract::The transcription factor NF-kappaB is a critical regulator of inflammatory and cell survival signals. Proteasomal degradation of NF-kappaB subunits plays an important role in the termination of NF-kappaB activity, and at least one of the identified ubiquitin ligases is a multimeric complex containing Copper Metabolism...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1748409

    authors: Mao X,Gluck N,Li D,Maine GN,Li H,Zaidi IW,Repaka A,Mayo MW,Burstein E

    更新日期:2009-04-01 00:00:00

  • Vein expression is induced by the EGF receptor pathway to provide a positive feedback loop in patterning the Drosophila embryonic ventral ectoderm.

    abstract::The presence of a single EGF receptor in Drosophila is contrasted by multiple ligands activating it. This work explores the role of two ligands, Spitz and Vein, in the embryonic ventral ectoderm. Spitz is a potent ligand, whereas Vein is an intrinsically weak activating ligand. We show that secreted Spitz emanating fr...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.13.2.158

    authors: Golembo M,Yarnitzky T,Volk T,Shilo BZ

    更新日期:1999-01-15 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

  • Direct recognition of initiator elements by a component of the transcription factor IID complex.

    abstract::A core promoter element called an initiator (Inr) overlaps the transcription start site of numerous mammalian protein-coding genes. In promoters that lack a TATA box, the Inr is functionally analogous to TATA, in that it is capable of directing basal transcription by RNA polymerase II and of determining the precise si...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.8.7.821

    authors: Kaufmann J,Smale ST

    更新日期:1994-04-01 00:00:00

  • USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation.

    abstract::The ubiquitin-specific protease (USP) family is the largest group of cysteine proteases. Cancer genomic analysis identified frequent amplification of USP21 (22%) in human pancreatic ductal adenocarcinoma (PDAC). USP21 overexpression correlates with human PDAC progression, and enforced expression of USP21 accelerates m...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.326314.119

    authors: Hou P,Ma X,Zhang Q,Wu CJ,Liao W,Li J,Wang H,Zhao J,Zhou X,Guan C,Ackroyd J,Jiang S,Zhang J,Spring DJ,Wang YA,DePinho RA

    更新日期:2019-10-01 00:00:00

  • The scaffold protein WRAP53β orchestrates the ubiquitin response critical for DNA double-strand break repair.

    abstract::The WD40 domain-containing protein WRAP53β (WD40 encoding RNA antisense to p53; also referred to as WDR79/TCAB1) controls trafficking of splicing factors and the telomerase enzyme to Cajal bodies, and its functional loss has been linked to carcinogenesis, premature aging, and neurodegeneration. Here, we identify WRAP5...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.246546.114

    authors: Henriksson S,Rassoolzadeh H,Hedström E,Coucoravas C,Julner A,Goldstein M,Imreh G,Zhivotovsky B,Kastan MB,Helleday T,Farnebo M

    更新日期:2014-12-15 00:00:00

  • DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint.

    abstract::Checkpoint genes maintain genomic stability by arresting cells after DNA damage. Many of these genes also control cell cycle events in unperturbed cells. By conducting a screen for checkpoint genes in zebrafish, we found that dtl/cdt2 is an essential component of the early, radiation-induced G2/M checkpoint. We subseq...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1482106

    authors: Sansam CL,Shepard JL,Lai K,Ianari A,Danielian PS,Amsterdam A,Hopkins N,Lees JA

    更新日期:2006-11-15 00:00:00

  • Selective elimination of the contact site A protein of Dictyostelium discoideum by gene disruption.

    abstract::The contact site A glycoprotein is a developmentally regulated cell-surface component expressed during the aggregation stage of Dictyostelium discoideum. This protein has been implicated in the EDTA-stable (Ca2(+)-independent) type of cell adhesion of aggregating cells. The gene coding for the contact site A protein w...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.3.12a.2011

    authors: Harloff C,Gerisch G,Noegel AA

    更新日期:1989-12-01 00:00:00

  • Voltage-gated potassium channel EAG2 controls mitotic entry and tumor growth in medulloblastoma via regulating cell volume dynamics.

    abstract::Medulloblastoma (MB) is the most common pediatric CNS malignancy. We identify EAG2 as an overexpressed potassium channel in MBs across different molecular and histological subgroups. EAG2 knockdown not only impairs MB cell growth in vitro, but also reduces tumor burden in vivo and enhances survival in xenograft studie...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.193789.112

    authors: Huang X,Dubuc AM,Hashizume R,Berg J,He Y,Wang J,Chiang C,Cooper MK,Northcott PA,Taylor MD,Barnes MJ,Tihan T,Chen J,Hackett CS,Weiss WA,James CD,Rowitch DH,Shuman MA,Jan YN,Jan LY

    更新日期:2012-08-15 00:00:00

  • The need for enhancers is acquired upon formation of a diploid nucleus during early mouse development.

    abstract::The activity of the polyoma virus (PyV) origin of DNA replication was used as a sensitive assay for enhancer function in one- and two-cell mouse embryos by injecting embryos with plasmid DNA containing different PyV ori configurations, allowing them to continue development in vitro, and then measuring plasmid DNA repl...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.2.9.1115

    authors: Martínez-Salas E,Cupo DY,DePamphilis ML

    更新日期:1988-09-01 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

  • Isolation of a cDNA encoding the largest subunit of TFIIA reveals functions important for activated transcription.

    abstract::Transcription factor IIA has been shown to interact with the TATA-binding protein and to act early during preinitiation complex formation. The human factor is composed of three subunits (alpha, beta, gamma). A human cDNA clone encoding the largest subunit of TFIIA (alpha) was isolated. The recombinant alpha polypeptid...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.7.11.2246

    authors: Ma D,Watanabe H,Mermelstein F,Admon A,Oguri K,Sun X,Wada T,Imai T,Shiroya T,Reinberg D

    更新日期:1993-11-01 00:00:00

  • Cap-independent translation of encephalomyocarditis virus RNA: structural elements of the internal ribosomal entry site and involvement of a cellular 57-kD RNA-binding protein.

    abstract::Translation of encephalomyocarditis virus (EMCV) mRNA occurs by ribosomal internal entry into the 5'-nontranslated region (5' NTR) rather than by ribosomal scanning. The internal ribosomal entry site (IRES) in the EMCV 5' NTR was determined by in vitro translation with RNAs that were generated by in vitro transcriptio...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.4.9.1560

    authors: Jang SK,Wimmer E

    更新日期:1990-09-01 00:00:00

  • Chromatin and nucleosome dynamics in DNA damage and repair.

    abstract::Chromatin is organized into higher-order structures that form subcompartments in interphase nuclei. Different categories of specialized enzymes act on chromatin and regulate its compaction and biophysical characteristics in response to physiological conditions. We present an overview of the function of chromatin struc...

    journal_title:Genes & development

    pub_type: 杂志文章,评审

    doi:10.1101/gad.307702.117

    authors: Hauer MH,Gasser SM

    更新日期:2017-11-15 00:00:00

  • Tumor suppression and normal aging in mice with constitutively high p53 activity.

    abstract::The p53 inhibitor murine double-minute gene 2 (Mdm2) is a target for potential cancer therapies, however increased p53 function can be lethal. To directly address whether reduced Mdm2 function can inhibit tumorigenesis without causing detrimental side effects, we exploited a hypomorphic murine allele of mdm2 to compar...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1378506

    authors: Mendrysa SM,O'Leary KA,McElwee MK,Michalowski J,Eisenman RN,Powell DA,Perry ME

    更新日期:2006-01-01 00:00:00

  • Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes.

    abstract::Eukaryotic RNAs with premature termination codons (PTCs) are eliminated by nonsense-mediated decay (NMD). While human nonsense RNA degradation can be initiated either by an endonucleolytic cleavage event near the PTC or through decapping, the individual contribution of these activities on endogenous substrates has rem...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.246538.114

    authors: Lykke-Andersen S,Chen Y,Ardal BR,Lilje B,Waage J,Sandelin A,Jensen TH

    更新日期:2014-11-15 00:00:00

  • rhomboid, a gene required for dorsoventral axis establishment and peripheral nervous system development in Drosophila melanogaster.

    abstract::rhomboid (rho) belongs to a group of four genes involved in the elaboration of positional information at a ventrolateral level in the Drosophila embryo. Mutations at any of these four loci also lead to a variety of other phenotypes, including reduction in the number of stretch receptor organs (chordotonal organs) in t...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.4.2.190

    authors: Bier E,Jan LY,Jan YN

    更新日期:1990-02-01 00:00:00