Abstract:
:Through as yet undefined proteins and pathways, the SUMO-targeted ubiquitin ligase (STUbL) suppresses genomic instability by ubiquitinating SUMO conjugated proteins and driving their proteasomal destruction. Here, we identify a critical function for fission yeast STUbL in suppressing spontaneous and chemically induced topoisomerase I (Top1)-mediated DNA damage. Strikingly, cells with reduced STUbL activity are dependent on tyrosyl-DNA phosphodiesterase 1 (Tdp1). This is notable, as cells lacking Tdp1 are largely aphenotypic in the vegetative cell cycle due to the existence of alternative pathways for the removal of covalent Top1-DNA adducts (Top1cc). We further identify Rad60, a SUMO mimetic and STUbL-interacting protein, and the SUMO E3 ligase Nse2 as critical Top1cc repair factors in cells lacking Tdp1. Detection of Top1ccs using chromatin immunoprecipitation and quantitative PCR shows that they are elevated in cells lacking Tdp1 and STUbL, Rad60, or Nse2 SUMO ligase activity. These unrepaired Top1ccs are shown to cause DNA damage, hyper-recombination, and checkpoint-mediated cell cycle arrest. We further determine that Tdp1 and the nucleotide excision repair endonuclease Rad16-Swi10 initiate the major Top1cc repair pathways of fission yeast. Tdp1-based repair is the predominant activity outside S phase, likely acting on transcription-coupled Top1cc. Epistasis analyses suggest that STUbL, Rad60, and Nse2 facilitate the Rad16-Swi10 pathway, parallel to Tdp1. Collectively, these results reveal a unified role for STUbL, Rad60, and Nse2 in protecting genome stability against spontaneous Top1-mediated DNA damage.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Heideker J,Prudden J,Perry JJ,Tainer JA,Boddy MNdoi
10.1371/journal.pgen.1001320subject
Has Abstractpub_date
2011-03-01 00:00:00pages
e1001320issue
3eissn
1553-7390issn
1553-7404journal_volume
7pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::MicroRNAs (miRNAs) post-transcriptionally regulate the expression of thousands of distinct mRNAs. While some regulatory interactions help to maintain basal cellular functions, others are likely relevant in more specific settings, such as response to stress. Here we describe such a role for the mir-290-295 cluster, the...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002054
更新日期:2011-05-01 00:00:00
abstract::Mating and gametogenesis are two essential components of animal reproduction. Gametogenesis must be modulated by the need for gametes, yet little is known of how mating, a process that utilizes gametes, may modulate the process of gametogenesis. Here, we report that mating stimulates female germline stem cell (GSC) pr...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006123
更新日期:2016-06-16 00:00:00
abstract::DNA double-strand breaks (DSBs) are one of the most dangerous DNA lesions, since their erroneous repair by nonhomologous end-joining (NHEJ) can generate harmful chromosomal rearrangements. PolX DNA polymerases are well suited to extend DSB ends that cannot be directly ligated due to their particular ability to bind to...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003656
更新日期:2013-01-01 00:00:00
abstract::Sodalis glossinidius, a maternally inherited endosymbiont of the tsetse fly, maintains genes encoding homologues of the PhoP-PhoQ two-component regulatory system. This two-component system has been extensively studied in facultative bacterial pathogens and is known to serve as an environmental magnesium sensor and a r...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002349
更新日期:2011-11-01 00:00:00
abstract::Identifying regions of positive selection in genomic data remains a challenge in population genetics. Most current approaches rely on comparing values of summary statistics calculated in windows. We present an approach termed SURFDAWave, which translates measures of genetic diversity calculated in genomic windows to f...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008896
更新日期:2020-08-27 00:00:00
abstract::The High Pathogenicity Island of Yersinia pseudotuberculosis IP32637 was previously shown to be horizontally transferable as part of a large chromosomal segment. We demonstrate here that at low temperature other chromosomal loci, as well as a non-mobilizable plasmid (pUC4K), are also transferable. This transfer, desig...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002529
更新日期:2012-01-01 00:00:00
abstract::A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differenti...
journal_title:PLoS genetics
pub_type: 杂志文章,评审
doi:10.1371/journal.pgen.1004601
更新日期:2014-08-28 00:00:00
abstract::Intragenomic conflicts arise when a genetic element favours its own transmission to the detriment of others. Conflicts over sex chromosome transmission are expected to have influenced genome structure, gene regulation, and speciation. In the mouse, the existence of an intragenomic conflict between X- and Y-linked mult...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002900
更新日期:2012-09-01 00:00:00
abstract::During organogenesis, PAX6 is required for establishment of various progenitor subtypes within the central nervous system, eye and pancreas. PAX6 expression is maintained in a variety of cell types within each organ, although its role in each lineage and how it acquires cell-specific activity remain elusive. Herein, w...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004360
更新日期:2014-05-29 00:00:00
abstract::During development of the cerebral cortex, neural stem cells (NSCs) divide symmetrically to proliferate and asymmetrically to generate neurons. Although faithful segregation of mitotic chromosomes is critical for NSC divisions, its fundamental mechanism remains unclear. A class of evolutionarily conserved protein comp...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004847
更新日期:2014-12-04 00:00:00
abstract::Previous genetic studies have suggested a history of sub-Saharan African gene flow into some West Eurasian populations after the initial dispersal out of Africa that occurred at least 45,000 years ago. However, there has been no accurate characterization of the proportion of mixture, or of its date. We analyze genome-...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001373
更新日期:2011-04-01 00:00:00
abstract::Genome integrity depends on correct chromosome segregation, which in turn relies on cohesion between sister chromatids from S phase until anaphase. S phase cohesion, together with DNA double-strand break (DSB) recruitment of cohesin and formation of damage-induced (DI) cohesion, has previously been shown to be require...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003158
更新日期:2013-01-01 00:00:00
abstract::Knowledge of the functional cis-regulatory elements that regulate constitutive and alternative pre-mRNA splicing is fundamental for biology and medicine. Here we undertook a genome-wide comparative genomics approach using available mammalian genomes to identify conserved intronic splicing regulatory elements (ISREs). ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0030085
更新日期:2007-05-25 00:00:00
abstract::Mimivirus and Megavirus are the best characterized representatives of an expanding new family of giant viruses infecting Acanthamoeba. Their most distinctive features, megabase-sized genomes carried in particles of size comparable to that of small bacteria, fill the gap between the viral and cellular worlds. These gia...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003122
更新日期:2012-01-01 00:00:00
abstract::The contributions of the Sgs1, Mph1, and Srs2 DNA helicases during mitotic double-strand break (DSB) repair in yeast were investigated using a gap-repair assay. A diverged chromosomal substrate was used as a repair template for the gapped plasmid, allowing mismatch-containing heteroduplex DNA (hDNA) formed during reco...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003340
更新日期:2013-01-01 00:00:00
abstract::RNA interference (RNAi) related pathways are essential for germline development and fertility in metazoa and can contribute to inter- and trans-generational inheritance. In the nematode Caenorhabditis elegans, environmental double-stranded RNA provided by feeding can lead to heritable changes in phenotype and gene exp...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007905
更新日期:2019-02-08 00:00:00
abstract::The nuclear lamina is the structural scaffold of the nuclear envelope and is well known for its central role in nuclear organization and maintaining nuclear stability and shape. In the past, a number of severe human disorders have been identified to be associated with mutations in lamins. Extensive research on this to...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003261
更新日期:2013-01-01 00:00:00
abstract::Cytosine methylation is an ancient epigenetic modification yet its function and extent within genomes is highly variable across eukaryotes. In mammals, methylation controls transposable elements and regulates the promoters of genes. In insects, DNA methylation is generally restricted to a small subset of transcribed g...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008864
更新日期:2020-06-25 00:00:00
abstract::Nephrolithiasis is a common nephrologic disorder with complex etiology. To identify the genetic factor(s) for nephrolithiasis, we conducted a three-stage genome-wide association study (GWAS) using a total of 5,892 nephrolithiasis cases and 17,809 controls of Japanese origin. Here we found three novel loci for nephroli...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002541
更新日期:2012-01-01 00:00:00
abstract::Most of the genetic architecture of schizophrenia (SCZ) has not yet been identified. Here, we apply a novel statistical algorithm called Covariate-Modulated Mixture Modeling (CM3), which incorporates auxiliary information (heterozygosity, total linkage disequilibrium, genomic annotations, pleiotropy) for each single n...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005803
更新日期:2016-01-25 00:00:00
abstract::Adaptive radiation is the rapid origination of multiple species from a single ancestor as the result of concurrent adaptation to disparate environments. This fundamental evolutionary process is considered to be responsible for the genesis of a great portion of the diversity of life. Bacteria have evolved enormous biol...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001296
更新日期:2011-02-10 00:00:00
abstract::In plants, multiple detached tissues are capable of forming a pluripotent cell mass, termed callus, when cultured on media containing appropriate plant hormones. Recent studies demonstrated that callus resembles the root-tip meristem, even if it is derived from aerial organs. This finding improves our understanding of...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002911
更新日期:2012-08-01 00:00:00
abstract::Although kinetochores normally play a key role in sister chromatid separation and segregation, chromosome fragments lacking kinetochores (acentrics) can in some cases separate and segregate successfully. In Drosophila neuroblasts, acentric chromosomes undergo delayed, but otherwise normal sister separation, revealing ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1009304
更新日期:2021-01-29 00:00:00
abstract::H1 linker histones facilitate higher-order chromatin folding and are essential for mammalian development. To achieve high-resolution mapping of H1 variants H1d and H1c in embryonic stem cells (ESCs), we have established a knock-in system and shown that the N-terminally tagged H1 proteins are functionally interchangeab...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003417
更新日期:2013-01-01 00:00:00
abstract::Biogenesis of mammalian mitochondrial ribosomes requires a concerted maturation of both the small (SSU) and large subunit (LSU). We demonstrate here that the m(5)C methyltransferase NSUN4, which forms a complex with MTERF4, is essential in mitochondrial ribosomal biogenesis as mitochondrial translation is abolished in...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004110
更新日期:2014-02-06 00:00:00
abstract::We resequenced and phased 27 kb of DNA within 580 kb of the MHC class II region in 158 population chromosomes, most of which were conserved extended haplotypes (CEHs) of European descent or contained their centromeric fragments. We determined the single nucleotide polymorphism and deletion-insertion polymorphism allel...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004637
更新日期:2014-10-09 00:00:00
abstract::rs143383 is a C to T transition SNP located in the 5'untranslated region (5'UTR) of the growth differentiation factor 5 gene GDF5. The T allele of the SNP is associated with increased risk of osteoarthritis (OA) in Europeans and in Asians. This susceptibility is mediated by the T allele producing less GDF5 transcript ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003557
更新日期:2013-06-01 00:00:00
abstract::Efficient adaptation to iron starvation is an essential virulence determinant of the most common human mold pathogen, Aspergillus fumigatus. Here, we demonstrate that the cytosolic monothiol glutaredoxin GrxD plays an essential role in iron sensing in this fungus. Our studies revealed that (i) GrxD is essential for gr...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008379
更新日期:2019-09-16 00:00:00
abstract::Fibroblasts are ubiquitous mesenchymal cells with many vital functions during development, tissue repair, and disease. Fibroblasts from different anatomic sites have distinct and characteristic gene expression patterns, but the principles that govern their molecular specialization are poorly understood. Spatial organi...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0020119
更新日期:2006-07-01 00:00:00
abstract::Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate the complexities of the genetic etiology of this heterogeneous condition, this factor remains incompletely understood. Here, we describe mutation...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006470
更新日期:2017-01-12 00:00:00