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 Devjournal_title
Genes & developmentauthors
McKinnon PJdoi
10.1101/gad.301325.117subject
Has Abstractpub_date
2017-06-15 00:00:00pages
1180-1194issue
12eissn
0890-9369issn
1549-5477pii
31/12/1180journal_volume
31pub_type
杂志文章,评审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
更新日期:2018-01-15 00:00:00
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
更新日期:1988-11-01 00:00:00
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
更新日期:2004-02-01 00:00:00
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
更新日期:2020-12-01 00:00:00
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
更新日期:1998-11-01 00:00:00
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
更新日期:1994-10-01 00:00:00
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
更新日期:1988-12-01 00:00:00
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
更新日期:2003-06-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2018511
更新日期:2011-02-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.311712.118
更新日期:2018-04-01 00:00:00
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
更新日期:1995-10-15 00:00:00
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
更新日期:2008-08-15 00:00:00
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
更新日期:1993-02-01 00:00:00
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
更新日期:2009-04-01 00:00:00
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
更新日期:1999-01-15 00:00:00
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
更新日期:2015-04-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.7.821
更新日期:1994-04-01 00:00:00
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
更新日期:2019-10-01 00:00:00
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
更新日期:2014-12-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1482106
更新日期:2006-11-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.12a.2011
更新日期:1989-12-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.193789.112
更新日期:2012-08-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.9.1115
更新日期:1988-09-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.288340.116
更新日期:2016-11-01 00:00:00
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
更新日期:1993-11-01 00:00:00
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
更新日期:1990-09-01 00:00:00
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
更新日期:2017-11-15 00:00:00
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
更新日期:2006-01-01 00:00:00
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
更新日期:2014-11-15 00:00:00
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
更新日期:1990-02-01 00:00:00