Dna2 processes behind the fork long ssDNA flaps generated by Pif1 and replication-dependent strand displacement

Dna2 is a DNA helicase-endonuclease mediating DSB resection and Okazaki fragment processing. Dna2 ablation is lethal and rescued by inactivation of Pif1, a helicase assisting Okazaki fragment maturation, Pol32, a DNA polymerase \u3b4 subunit, and Rad9, a DNA damage response (DDR) factor. Dna2 counteracts fork reversal and promotes fork restart. Here we show that Dna2 depletion generates lethal DNA structures activating the DDR. While PIF1 deletion rescues the lethality of Dna2 depletion, RAD9 ablation relieves the first cell cycle arrest causing genotoxicity after few cell divisions. Slow fork speed attenuates DDR in Dna2 deprived cells. Electron microscopy shows that Dna2-ablated cells accumulate long ssDNA flaps behind the forks through Pif1 and fork speed. We suggest that Dna2 offsets the strand displacement activity mediated by the lagging strand polymerase and Pif1, processing long ssDNA flaps to prevent DDR activation. We propose that this Dna2 function has been hijacked by Break Induced Replication in DSB processing

INTERPLAY BETWEEN THE DNA HELICASES PIF1 AND RRM3, THE NUCLEASE DNA2 AND THE CHECKPOINT PATHWAYS IN THE MAINTENANCE OF THE DNA REPLICATION FORK INTEGRITY

Eukaryotic cells have evolved the ATR/hCHK1, MEC1/RAD53 kinase-mediated signal transduction pathway, known as replication checkpoint, to protect and stabilize stalled replication forks in human cells and budding yeasts, respectively. rad53 mutants, exposed to high doses of the DNA replication inhibitor hydroxyurea (HU), accumulate hemireplicated, gapped and reversed forks, while treatments with low HU doses induce massive chromosome fragmentation. The aim of my work was to better understand the molecular mechanisms through which Rad53 prevents unusual alterations of the architecture of the stalled replication forks and chromosome fragility, under replication stress. We revealed that Rrm3 and Pif1, DNA helicases assisting fork progression across pausing sites in unperturbed conditions, are detrimental in rad53 mutants experiencing HU-induced replication stress. Rrm3 and Pif1 ablation synergistically rescues cell lethality, chromosome fragmentation, replisome dissociation, fork reversal and ssDNA gaps formation at the forks of rad53 cells exposed to replication stress. We provide evidence that Pif1 and Rrm3 associate with stalled DNA replication forks and are regulated through Rad53-mediated phosphorylation. Our findings uncover a new replication-stress-induced regulative loop in which Rad53 down regulates the Pif1 DNA helicases at the stalled replication forks. In the second part of this thesis we examined the crosstalk between Rrm3, Pif1, the mediator of the DNA damage checkpoint Rad9 and the nuclease Dna2, during unperturbed DNA replication. The experimental evidence collected in this second part of the project, together with pioneering work previously reported from other laboratories, strongly suggests that Dna2, Pif1 and Rrm3 cooperate to finalize late stages of DNA replication

Baryon Junction Stopping at the SPS and RHIC via HIJING/B

Baryon stopping at the SPS and RHIC energies is calculated by introducing a new baryon junction mechanism into HIJING. The exchange of a baryon junction, according to Regge phenomenology, leads to a cosh(y/2) rapidity dependence and an s^(-1/4) energy dependence of the inclusive baryon cross section. This baryon junction dynamics also leads naturally to enhanced p_T broadening in pA and AA together with enhanced mid-rapidity hyperon production.Comment: Proceedings for Quark Matter 97; 4 pages, 1 eps-figur

Baryon Number Fluctuation and the Quark-Gluon Plasma

We show that $\omega_B$ or $\omega_{\bar B}$, the squared baryon or antibaryon number fluctuation per baryon or antibaryon, is a possible signature for the quark-gluon plasma that is expected to be created in relativistic heavy ion collisions, as it is a factor of three smaller than in an equilibrated hadronic matter due to the fractional baryon number of quarks. Using kinetic equations with exact baryon number conservation, we find that their values in an equilibrated matter are half of those expected from a Poisson distribution. Effects due to finite acceptance and non-zero net baryon number are also studied.Comment: discussion and references added, version to appear in PR

Pengaruh Work From Home Terhadap Kinerja Karyawan Dengan Internal Motivation dan Organizational Trust Sebagai Variabel Mediasi (Perwakilan Karyawan Telkom Group di Telkom Regional IV Jateng dan DIY)

This research aims to analyze the influence of work from home on employee performance with internal motivation and organizational trust as a mediation variable in Telkom Group Employee Representatives in Telkom Regional IV Jateng and DIY. The type of research used in this study is Conformatory Factor Analysis (CFA) with a quantitative approach. The sampling method used is Proposive Sampling. The population or object in the selected research is all employees of Telkom Group Employee Representatives in Telkom Regional IV Jateng and DIY with the criteria of having implemented work from home (WFH) work system practices. The number of employees who meet these criteria is as many as 100 people with the distribution of WFH rations that have been regulated by the agency. Method of collecting data by spreading questionnaires online using google form links. Data analysis uses instrument tests, classical assumption tests, hypothesis tests, and Structural Equation Modeling (SEM) analysis using the Smart PLS 3.0 program. The results showed that the practice of work from home system did not have a positive and significant effect on employee performance. While internal motivation and organizational trust as mediation between work from home and employee performance has a significant positive effect

Matter-Antimatter Asymmetry in the Large Hadron Collider

The matter-antimatter asymmetry is one of the greatest challenges in the modern physics. The universe including this paper and even the reader him(her)self seems to be built up of ordinary matter only. Theoretically, the well-known Sakharov's conditions remain the solid framework explaining the circumstances that matter became dominant against the antimatter while the universe cools down and/or expands. On the other hand, the standard model for elementary particles apparently prevents at least two conditions out of them. In this work, we introduce a systematic study of the antiparticle-to-particle ratios measured in various $NN$ and $AA$ collisions over the last three decades. It is obvious that the available experimental facilities turn to be able to perform nuclear collisions, in which the matter-antimatter asymmetry raises from $\sim 0$ at AGS to $\sim 100$ at LHC. Assuming that the final state of hadronization in the nuclear collisions takes place along the freezeout line, which is defined by a constant entropy density, various antiparticle-to-particle ratios are studied in framework of the hadron resonance gas (HRG) model. Implementing modified phase space and distribution function in the grand-canonical ensemble and taking into account the experimental acceptance, the ratios of antiparticle-to-particle over the whole range of center-of-mass-energies are very well reproduced by the HRG model. Furthermore, the antiproton-to-proton ratios measured by ALICE in $pp$ collisions is also very well described by the HRG model. It is likely to conclude that the LHC heavy-ion program will produce the same particle ratios as the $pp$ program implying the dynamics and evolution of the system would not depend on the initial conditions. The ratios of bosons and baryons get very close to unity indicating that the matter-antimatter asymmetry nearly vanishes at LHC.Comment: 9 pages, 5 eps-figures, revtex4-styl

Jet Quenching and the p-bar >= pi- Anomaly at RHIC

PHENIX data on Au+Au at root(s)_= 130 AGeV suggest that p-bar yields may exceed pi- at high p_T > 2 GeV/c. We propose that jet quenching in central collisions suppresses the hard PQCD component of the spectra in central A+A reactions, thereby exposing a novel component of baryon dynamics that we attribute to (gluonic) baryon junctions. We predict that the observed p-bar >= pi- and the p > pi+ anomaly at p_T ~ 2 GeV/c is limited to a finite p_T window that decreases with increasing impact parameter.Comment: 5 pages, 4 figures, REVTeX, uses bbox.sty. Final version: references and figures updated. Added discussion on the p/pi+ rati

Last Call for RHIC Predictions

This paper contains the individual contributions of all speakers of the session on 'Last Call for RHIC Predictions' at Quark Matter 99, and a summary by the convenor.Comment: 56 pages, psfig, epsf, epsfig, graphicx style files required, Proceedings of the XIV Int. Conf. on Nucleus-Nucleus Collisions, Quark Matter 99, Torino, Italy, May 10 - 15, 1999. Typographical mistakes corrected and figure numbers change

Critical exponents and equation of state of the three-dimensional Heisenberg universality class

We improve the theoretical estimates of the critical exponents for the three-dimensional Heisenberg universality class. We find gamma=1.3960(9), nu=0.7112(5), eta=0.0375(5), alpha=-0.1336(15), beta=0.3689(3), and delta=4.783(3). We consider an improved lattice phi^4 Hamiltonian with suppressed leading scaling corrections. Our results are obtained by combining Monte Carlo simulations based on finite-size scaling methods and high-temperature expansions. The critical exponents are computed from high-temperature expansions specialized to the phi^4 improved model. By the same technique we determine the coefficients of the small-magnetization expansion of the equation of state. This expansion is extended analytically by means of approximate parametric representations, obtaining the equation of state in the whole critical region. We also determine a number of universal amplitude ratios.Comment: 40 pages, final version. In publication in Phys. Rev.