133 research outputs found
Essential and checkpoint functions of budding yeast ATM and ATR during meiotic prophase are facilitated by differential phosphorylation of a meiotic adaptor protein, Hop1
A hallmark of the conserved ATM/ATR signalling is its ability to mediate a wide range of functions utilizing only a limited number of adaptors and effector kinases. During meiosis, Tel1 and Mec1, the budding yeast ATM and ATR, respectively, rely on a meiotic adaptor protein Hop1, a 53BP1/Rad9 functional analog, and its associated kinase Mek1, a CHK2/Rad53-paralog, to mediate multiple functions: control of the formation and repair of programmed meiotic DNA double strand breaks, enforcement of inter-homolog bias, regulation of meiotic progression, and implementation of checkpoint responses. Here, we present evidence that the multi-functionality of the Tel1/Mec1-to-Hop1/Mek1 signalling depends on stepwise activation of Mek1 that is mediated by Tel1/Mec1 phosphorylation of two specific residues within Hop1: phosphorylation at the threonine 318 (T318) ensures the transient basal level Mek1 activation required for viable spore formation during unperturbed meiosis. Phosphorylation at the serine 298 (S298) promotes stable Hop1-Mek1 interaction on chromosomes following the initial phospho-T318 mediated Mek1 recruitment. In the absence of Dmc1, the phospho-S298 also promotes Mek1 hyper-activation necessary for implementing meiotic checkpoint arrest. Taking these observations together, we propose that the Hop1 phospho-T318 and phospho-S298 constitute key components of the Tel1/Mec1- based meiotic recombination surveillance (MRS) network and facilitate effective coupling of meiotic recombination and progression during both unperturbed and challenged meiosis
Multiplicity and transverse momentum fluctuations in inelastic proton-proton interactions at the CERN Super Proton Synchrotron
Measurements of multiplicity and transverse momentum fluctuations of charged
particles were performed in inelastic p+p interactions at 20, 31, 40, 80 and
158 GeV/c beam momentum. Results for the scaled variance of the multiplicity
distribution and for three strongly intensive measures of multiplicity and
transverse momentum fluctuations \$\Delta[P_{T},N]\$, \$\Sigma[P_{T},N]\$ and
\$\Phi_{p_T}\$ are presented. For the first time the results on fluctuations
are fully corrected for experimental biases. The results on multiplicity and
transverse momentum fluctuations significantly deviate from expectations for
the independent particle production. They also depend on charges of selected
hadrons. The string-resonance Monte Carlo models EPOS and UrQMD do not describe
the data. The scaled variance of multiplicity fluctuations is significantly
higher in inelastic p+p interactions than in central Pb+Pb collisions measured
by NA49 at the same energy per nucleon. This is in qualitative disagreement
with the predictions of the Wounded Nucleon Model. Within the statistical
framework the enhanced multiplicity fluctuations in inelastic p+p interactions
can be interpreted as due to event-by-event fluctuations of the fireball energy
and/or volume.Comment: 18 pages, 12 figure
Pion emission from the T2K replica target: method, results and application
The T2K long-baseline neutrino oscillation experiment in Japan needs precise
predictions of the initial neutrino flux. The highest precision can be reached
based on detailed measurements of hadron emission from the same target as used
by T2K exposed to a proton beam of the same kinetic energy of 30 GeV. The
corresponding data were recorded in 2007-2010 by the NA61/SHINE experiment at
the CERN SPS using a replica of the T2K graphite target. In this paper details
of the experiment, data taking, data analysis method and results from the 2007
pilot run are presented. Furthermore, the application of the NA61/SHINE
measurements to the predictions of the T2K initial neutrino flux is described
and discussed.Comment: updated version as published by NIM
Measurements of , , , and proton production in proton-carbon interactions at 31 GeV/ with the NA61/SHINE spectrometer at the CERN SPS
Measurements of hadron production in p+C interactions at 31 GeV/c are
performed using the NA61/ SHINE spectrometer at the CERN SPS. The analysis is
based on the full set of data collected in 2009 using a graphite target with a
thickness of 4% of a nuclear interaction length. Inelastic and production cross
sections as well as spectra of , , p, and are
measured with high precision. These measurements are essential for improved
calculations of the initial neutrino fluxes in the T2K long-baseline neutrino
oscillation experiment in Japan. A comparison of the NA61/SHINE measurements
with predictions of several hadroproduction models is presented.Comment: v1 corresponds to the preprint CERN-PH-EP-2015-278; v2 matches the
final published versio
Measurement of negatively charged pion spectra in inelastic p+p interactions at = 20, 31, 40, 80 and 158 GeV/c
We present experimental results on inclusive spectra and mean multiplicities
of negatively charged pions produced in inelastic p+p interactions at incident
projectile momenta of 20, 31, 40, 80 and 158 GeV/c ( 6.3, 7.7,
8.8, 12.3 and 17.3 GeV, respectively). The measurements were performed using
the large acceptance NA61/SHINE hadron spectrometer at the CERN Super Proton
Synchrotron.
Two-dimensional spectra are determined in terms of rapidity and transverse
momentum. Their properties such as the width of rapidity distributions and the
inverse slope parameter of transverse mass spectra are extracted and their
collision energy dependences are presented. The results on inelastic p+p
interactions are compared with the corresponding data on central Pb+Pb
collisions measured by the NA49 experiment at the CERN SPS.
The results presented in this paper are part of the NA61/SHINE ion program
devoted to the study of the properties of the onset of deconfinement and search
for the critical point of strongly interacting matter. They are required for
interpretation of results on nucleus-nucleus and proton-nucleus collisions.Comment: Numerical results available at: https://edms.cern.ch/document/1314605
Updates in v3: Updated version, as accepted for publicatio
Measurement of Production Properties of Positively Charged Kaons in Proton-Carbon Interactions at 31 GeV/c
Spectra of positively charged kaons in p+C interactions at 31 GeV/c were
measured with the NA61/SHINE spectrometer at the CERN SPS. The analysis is
based on the full set of data collected in 2007 with a graphite target with a
thickness of 4% of a nuclear interaction length. Interaction cross sections and
charged pion spectra were already measured using the same set of data. These
new measurements in combination with the published ones are required to improve
predictions of the neutrino flux for the T2K long baseline neutrino oscillation
experiment in Japan. In particular, the knowledge of kaon production is crucial
for precisely predicting the intrinsic electron neutrino component and the high
energy tail of the T2K beam. The results are presented as a function of
laboratory momentum in 2 intervals of the laboratory polar angle covering the
range from 20 up to 240 mrad. The kaon spectra are compared with predictions of
several hadron production models. Using the published pion results and the new
kaon data, the K+/\pi+ ratios are computed.Comment: 10 pages, 11 figure
Measurements of , K, p and spectra in proton-proton interactions at 20, 31, 40, 80 and 158 GeV/c with the NA61/SHINE spectrometer at the CERN SPS
Measurements of inclusive spectra and mean multiplicities of ,
K, p and produced in inelastic p+p interactions at
incident projectile momenta of 20, 31, 40, 80 and 158 GeV/c ( 6.3,
7.7, 8.8, 12.3 and 17.3 GeV, respectively) were performed at the CERN Super
Proton Synchrotron using the large acceptance NA61/SHINE hadron spectrometer.
Spectra are presented as function of rapidity and transverse momentum and are
compared to predictions of current models. The measurements serve as the
baseline in the NA61/SHINE study of the properties of the onset of
deconfinement and search for the critical point of strongly interacting matter
Differing Requirements for RAD51 and DMC1 in Meiotic Pairing of Centromeres and Chromosome Arms in Arabidopsis thaliana
During meiosis homologous chromosomes pair, recombine, and synapse, thus ensuring accurate chromosome segregation and the halving of ploidy necessary for gametogenesis. The processes permitting a chromosome to pair only with its homologue are not fully understood, but successful pairing of homologous chromosomes is tightly linked to recombination. In Arabidopsis thaliana, meiotic prophase of rad51, xrcc3, and rad51C mutants appears normal up to the zygotene/pachytene stage, after which the genome fragments, leading to sterility. To better understand the relationship between recombination and chromosome pairing, we have analysed meiotic chromosome pairing in these and in dmc1 mutant lines. Our data show a differing requirement for these proteins in pairing of centromeric regions and chromosome arms. No homologous pairing of mid-arm or distal regions was observed in rad51, xrcc3, and rad51C mutants. However, homologous centromeres do pair in these mutants and we show that this does depend upon recombination, principally on DMC1. This centromere pairing extends well beyond the heterochromatic centromere region and, surprisingly, does not require XRCC3 and RAD51C. In addition to clarifying and bringing the roles of centromeres in meiotic synapsis to the fore, this analysis thus separates the roles in meiotic synapsis of DMC1 and RAD51 and the meiotic RAD51 paralogs, XRCC3 and RAD51C, with respect to different chromosome domains
Effective transcription factor binding site prediction using a combination of optimization, a genetic algorithm and discriminant analysis to capture distant interactions
<p>Abstract</p> <p>Background</p> <p>Reliable transcription factor binding site (TFBS) prediction methods are essential for computer annotation of large amount of genome sequence data. However, current methods to predict TFBSs are hampered by the high false-positive rates that occur when only sequence conservation at the core binding-sites is considered.</p> <p>Results</p> <p>To improve this situation, we have quantified the performance of several Position Weight Matrix (PWM) algorithms, using exhaustive approaches to find their optimal length and position. We applied these approaches to bio-medically important TFBSs involved in the regulation of cell growth and proliferation as well as in inflammatory, immune, and antiviral responses (NF-ΞΊB, ISGF3, IRF1, STAT1), obesity and lipid metabolism (PPAR, SREBP, HNF4), regulation of the steroidogenic (SF-1) and cell cycle (E2F) genes expression. We have also gained extra specificity using a method, entitled SiteGA, which takes into account structural interactions within TFBS core and flanking regions, using a genetic algorithm (GA) with a discriminant function of locally positioned dinucleotide (LPD) frequencies.</p> <p>To ensure a higher confidence in our approach, we applied resampling-jackknife and bootstrap tests for the comparison, it appears that, optimized PWM and SiteGA have shown similar recognition performances. Then we applied SiteGA and optimized PWMs (both separately and together) to sequences in the Eukaryotic Promoter Database (EPD). The resulting SiteGA recognition models can now be used to search sequences for BSs using the web tool, SiteGA.</p> <p>Analysis of dependencies between close and distant LPDs revealed by SiteGA models has shown that the most significant correlations are between close LPDs, and are generally located in the core (footprint) region. A greater number of less significant correlations are mainly between distant LPDs, which spanned both core and flanking regions. When SiteGA and optimized PWM models were applied together, this substantially reduced false positives at least at higher stringencies.</p> <p>Conclusion</p> <p>Based on this analysis, SiteGA adds substantial specificity even to optimized PWMs and may be considered for large-scale genome analysis. It adds to the range of techniques available for TFBS prediction, and EPD analysis has led to a list of genes which appear to be regulated by the above TFs.</p
Frequent and Efficient Use of the Sister Chromatid for DNA Double-Strand Break Repair during Budding Yeast Meiosis
Studies of DNA double-strand break repair during meiosis reveal that a substantial fraction of recombination occurs between sister chromatids
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