Abstract:
:During S phase, the entire genome must be precisely duplicated, with no sections of DNA left unreplicated. Here, we develop a simple mathematical model to describe the probability of replication failing due to the irreversible stalling of replication forks. We show that the probability of complete genome replication is maximized if replication origins are evenly spaced, the largest inter-origin distances are minimized, and the end-most origins are positioned close to chromosome ends. We show that origin positions in the yeast Saccharomyces cerevisiae genome conform to all three predictions thereby maximizing the probability of complete replication if replication forks stall. Origin positions in four other yeasts-Kluyveromyces lactis, Lachancea kluyveri, Lachancea waltii and Schizosaccharomyces pombe-also conform to these predictions. Equating failure rates at chromosome ends with those in chromosome interiors gives a mean per nucleotide fork stall rate of ∼5 × 10(-8), which is consistent with experimental estimates. Using this value in our theoretical predictions gives replication failure rates that are consistent with data from replication origin knockout experiments. Our theory also predicts that significantly larger genomes, such as those of mammals, will experience a much greater probability of replication failure genome-wide, and therefore will likely require additional compensatory mechanisms.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Newman TJ,Mamun MA,Nieduszynski CA,Blow JJdoi
10.1093/nar/gkt728subject
Has Abstractpub_date
2013-11-01 00:00:00pages
9705-18issue
21eissn
0305-1048issn
1362-4962pii
gkt728journal_volume
41pub_type
杂志文章abstract::Tight cell-cycle regulation of the histone H4-K20 methyltransferase PR-Set7 is essential for the maintenance of genome integrity. In mammals, this mainly involves the interaction of PR-Set7 with the replication factor PCNA, which triggers the degradation of the enzyme by the CRL4CDT2 E3 ubiquitin ligase. PR-Set7 is al...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky034
更新日期:2018-04-06 00:00:00
abstract::During protein synthesis, ribosomes become stalled on polyproline-containing sequences, unless they are rescued in archaea and eukaryotes by the initiation factor 5A (a/eIF-5A) and in bacteria by the homologous protein EF-P. While a structure of EF-P bound to the 70S ribosome exists, structural insight into eIF-5A on ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv1517
更新日期:2016-02-29 00:00:00
abstract::Mitotic chromosome structure is pivotal to cell division but difficult to observe in fine detail using conventional methods. DNA catenation has been implicated in both sister chromatid cohesion and chromosome condensation, but has never been observed directly. We have used a lab-on-a-chip microfluidic device and fluor...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks931
更新日期:2012-12-01 00:00:00
abstract::The MIPS Fusarium graminearum Genome Database (FGDB) is a comprehensive genome database on one of the most devastating fungal plant pathogens of wheat and barley. FGDB provides information on two gene sets independently derived by automated annotation of the F.graminearum genome sequence. A complete manually revised g...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkj026
更新日期:2006-01-01 00:00:00
abstract::BRENDA is a comprehensive relational database on functional and molecular information of enzymes, based on primary literature. The database contains information extracted and evaluated from approximately 46 000 references, holding data of at least 40 000 different enzymes from more than 6900 different organisms, class...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/30.1.47
更新日期:2002-01-01 00:00:00
abstract::We have studied the role of the C-terminal domain of the alpha subunit (alphaCTD) of Escherichia coli RNA polymerase during transcription initiation at promoters lacking an UP-element. The temperature requirement for open complex formation was used as an indication of the kinetics of this process. We have previously s...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.9.2051
更新日期:1999-05-01 00:00:00
abstract::We have recently developed a novel method for the affinity purification of the complete suite of translating mRNA from genetically labeled cell populations. This method permits comprehensive quantitative comparisons of the genes employed by each specific cell type. We provide a detailed description of tools for analys...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq130
更新日期:2010-07-01 00:00:00
abstract::The Dnd (DNA degradation) phenotype, reflecting a novel DNA modification by sulfur in Streptomyces lividans 1326, was strongly aggravated when one (dndB) of the five genes (dndABCDE) controlling it was mutated. Electrophoretic banding patterns of a plasmid (pHZ209), reflecting DNA degradation, displayed a clear change...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm176
更新日期:2007-01-01 00:00:00
abstract::The final step in the maturation of paramyxoviruses, orthomyxoviruses and viruses of several other families, entails the budding of the viral nucleocapsid through the plasma membrane of the host cell. Many medically important viruses, such as influenza, parainfluenza, respiratory syncytial virus (RSV) and Ebola, can f...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm246
更新日期:2007-01-01 00:00:00
abstract::Present results provide direct evidence of the nature of a conformational change in DNA when nucleosomes are formed from core histones and poly [d(A-T)]. First, we have found some features which have characteristic aspects of the A like conformation of DNA. Thus, an increased contribution due to a sugar conformation c...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/9.19.4879
更新日期:1981-10-10 00:00:00
abstract::Ribosome-inactivating proteins (RIPs) inhibit protein synthesis by enzymatically depurinating a specific adenine residue at the sarcin-ricin loop of the 28S rRNA, which thereby prevents the binding of elongation factors to the GTPase activation centre of the ribosome. Here, we present the 2.2 A crystal structure of tr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn922
更新日期:2009-02-01 00:00:00
abstract::Current approaches to design efficient antisense RNAs (asRNAs) rely primarily on a thermodynamic understanding of RNA-RNA interactions. However, these approaches depend on structure predictions and have limited accuracy, arguably due to overlooking important cellular environment factors. In this work, we develop a bio...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx115
更新日期:2017-05-19 00:00:00
abstract::Nucleotide sequences of three cloned restriction fragments of Tetrahymena mtDNA which showed hybridization with mitochondrial tRNA have been determined. EcoRI fragment 5 (4.1 kbp) contains the tRNAphe gene sequence with anticodon GAA; Hind III fragment 6 (2.0 kbp) the tRNAhis with anticodon GTG; and EcoRI fragment 7 (...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/13.9.3273
更新日期:1985-05-10 00:00:00
abstract::Unmodified tRNA molecules are useful for many purposes in cell-free protein biosynthesis, but there is little information about how the lack of tRNA post-transcriptional modifications affects the coding specificity for synonymous codons. In the present study, we prepared an unmodified form of Escherichia coli tRNA1Ser...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.15.2894
更新日期:1996-08-01 00:00:00
abstract::Treatment of the ciliated protozoan Tetrahymena thermophila with 8-methoxypsoralen combined with long wavelength ultraviolet irradiation (UVA, lambda approximately 360 nm) resulted in a dose dependent equal inhibition of the synthesis of rRNA, 5.8S, 5S and tRNA. Similar results were obtained with 3-carbethoxy-8-methox...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.3.921
更新日期:1987-02-11 00:00:00
abstract::Southern blot analyses using reduced stringency hybridization conditions have been employed to search for sequence homologies between rodent VL30 genes and murine leukemia virus (MuLV) proviruses. These constitute two classes of transposon-like elements previously believed to be genetically unrelated. Our results demo...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/11.2.305
更新日期:1983-01-25 00:00:00
abstract::G-quadruplexes are dynamic structures folded in G-rich single-stranded DNA regions. These structures have been recognized as a potential nucleic acid based mechanism for regulating multiple cellular processes such as replication, transcription and genomic maintenance. So far, their transcriptional role in vivo during ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw011
更新日期:2016-05-19 00:00:00
abstract::Reversion of T type cytoplasmic male sterility (cmsT) to fertility is correlated with sequence changes in a 1.5 kb AvaI fragment. This 1.5 kb AvaI fragment is composed of 5' flanking sequences of ATPase subunit 6, one complete open reading frame (ORF 13) and part of the another (ORF 25). The sequence of the 1.5 kb Ava...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.15.6091
更新日期:1987-08-11 00:00:00
abstract::Substantial amounts of DNA (at least 25 microgram per cm2) can be stably bound to diazobenzyloxymethyl (DBM)-paper. Complementary RNA will hybridize to the DNA paper almost completely in 24 hours. Using several different conditions of hybridization and washing, the background of RNA bound non-specifically is very low ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/6.1.195
更新日期:1979-01-01 00:00:00
abstract::Modification of cytosine plays an important role in epigenetic regulation of gene expression and genome stability. Cytosine is converted to 5-methylcytosine (5mC) by DNA methyltransferase; in turn, 5mC may be oxidized to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation enzyme. The structural flexibility of D...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa1210
更新日期:2021-01-25 00:00:00
abstract::DNA target recognizing domains of different multispecific DNA-cytosine-methyltransferases can be rearranged through engineering of the corresponding genes to generate enzymes with novel combinations of target recognition. ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/16.14.6649
更新日期:1988-07-25 00:00:00
abstract::The RDM1 gene encodes a RNA recognition motif (RRM)-containing protein involved in the cellular response to the anti-cancer drug cisplatin in vertebrates. We previously reported a cDNA encoding the full-length human RDM1 protein. Here, we describe the identification of 11 human cDNAs encoding RDM1 protein isoforms. Th...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm753
更新日期:2007-01-01 00:00:00
abstract::The Galaxy HiCExplorer provides a web service at https://hicexplorer.usegalaxy.eu. It enables the integrative analysis of chromosome conformation by providing tools and computational resources to pre-process, analyse and visualize Hi-C, Capture Hi-C (cHi-C) and single-cell Hi-C (scHi-C) data. Since the last publicatio...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa220
更新日期:2020-07-02 00:00:00
abstract::Period2 (Per2) is an essential component of the mammalian clock mechanism and robust circadian expression of Per2 is essential for the maintenance of circadian rhythms. Although recent studies have shown that the circadian E2 enhancer (a non-canonical E-box) accounts for most of the circadian transcriptional drive of ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl868
更新日期:2007-01-01 00:00:00
abstract::Prior work has indicated that an octanucleotide [5'TATAAGTA(+1)3'] sequence is used as a promoter in yeast mitochondria. Two such sequences (FP1 and FP2) are present upstream of the tRNA(fMet)-RNAse P RNA -tRNA(Pro) gene cluster but only the FP1 promoter but not the FP2 appears to be active in vivo and in vitro. The r...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.21.5937
更新日期:1991-11-11 00:00:00
abstract::The effect of several rifamycin derivatives on poly(A) synthesis in vitro was tested using purified rat liver mitochondrial poly(A) polymerase assayed with an exogenous primer. When used at a concentration of 300 mug/ml, derivatives AF/013, PR/19, AF/AETP, M/88 and AF/ABDP completely inhibited activity corresponding t...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/1.11.1549
更新日期:1974-11-01 00:00:00
abstract::For the isolation of single stranded plasmid DNA, various E. coli and E. coli-Streptomyces shuttle plasmids were equipped with the phage f1 replication origin. The transformation of some representative Streptomyces species with plasmid vectors occurred irrespective of whether single or double stranded DNA was used. In...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.4.727
更新日期:1991-02-25 00:00:00
abstract::The European Bioinformatics Institute (EMBL-EBI) supports life-science research throughout the world by providing open data, open-source software and analytical tools, and technical infrastructure (https://www.ebi.ac.uk). We accommodate an increasingly diverse range of data types and integrate them, so that biologists...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx1154
更新日期:2018-01-04 00:00:00
abstract::Detection of cell-free DNA in liquid biopsies offers great potential for use in non-invasive prenatal testing and as a cancer biomarker. Fetal and tumor DNA fractions however can be extremely low in these samples and ultra-sensitive methods are required for their detection. Here, we report an extremely simple and fast...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw224
更新日期:2016-06-20 00:00:00
abstract::Bacterial transcription factors often function as DNA-binding proteins that selectively activate or repress promoters, although the biochemical mechanisms vary. In most well-understood examples, activators function by either increasing the affinity of RNA polymerase (RNAP) for the target promoter, or by increasing the...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr1280
更新日期:2012-04-01 00:00:00