Rad62 protein functionally and physically associates with the Smc5/Smc6 protein complex and is required for chromosome integrity and recombination repair in fission yeast

Smc5 and Smc6 proteins form a heterodimeric SMC (structural maintenance of chromosome) protein complex like SMC1-SMC3 cohesin and SMC2-SMC4 condensin, and they associate with non-SMC proteins Nse1 and Nse2 stably and Rad60 transiently. This multiprotein complex plays an essential role in maintaining chromosome integrity and repairing DNA double strand breaks (DSBs). This study characterizes a Schizosaccharomyces pombe mutant rad62-1, which is hypersensitive to methyl methanesulfonate (MMS) and synthetically lethal with rad2 (a feature of recombination mutants). rad62-1 is hypersensitive to UV and gamma rays, epistatic with rhp51, and defective in repair of DSBs. rad62 is essential for viability and genetically interacts with rad60, smc6, and brc1. Rad62 protein physically associates with the Smc5-6 complex. rad62-1 is synthetically lethal with mutations in the genes promoting recovery from stalled replication, such as rqh1, srs2, and mus81, and those involved in nucleotide excision repair like rad13 and rad16. These results suggest that Rad62, like Rad60, in conjunction with the Smc5-6 complex, plays an essential role in maintaining chromosome integrity and recovery from stalled replication by recombination

RAD6-RAD18-RAD5-pathway-dependent tolerance to chronic low-dose ultraviolet light

In nature, organisms are exposed to chronic low- dose ultraviolet light ( CLUV) as opposed to the acute high doses common to laboratory experiments. Analysis of the cellular response to acute high-dose exposure has delineated the importance of direct DNA repair by the nucleotide excision repair pathway(1) and for checkpoint-induced cell cycle arrest in promoting cell survival(2). Here we examine the response of yeast cells to CLUV and identify a key role for the RAD6-RAD18-RAD5 error- free postreplication repair (RAD6 error-free PRR) pathway(3,4) in promoting cell growth and survival. We show that loss of the RAD6 error- free PRR pathway results in DNA-damage-checkpoint- induced G2 arrest in CLUV-exposed cells, whereas wild-type and nucleotide-excision-repair-deficient cells are largely unaffected. Cell cycle arrest in the absence of the RAD6 error- free PRR pathway was not caused by a repair defect or by the accumulation of ultraviolet-induced photoproducts. Notably, we observed increased replication protein A (RPA) and Rad52 - yellow fluorescent protein foci(5) in the CLUV- exposed rad18 Delta cells and demonstrated that Rad52- mediated homologous recombination is required for the viability of the rad18 Delta cells after release from CLUV- induced G2 arrest. These and other data presented suggest that, in response to environmental levels of ultraviolet exposure, the RAD6 error- free PRR pathway promotes replication of damaged templates without the generation of extensive single- stranded DNA regions. Thus, the error- free PRR pathway is specifically important during chronic low- dose ultraviolet exposure to prevent counter- productive DNA checkpoint activation and allow cells to proliferate normally

Specific recognition of a multiply phosphorylated motif in the DNA repair scaffold XRCC1 by the FHA domain of human PNK.

Short-patch repair of DNA single-strand breaks and gaps (SSB) is coordinated by XRCC1, a scaffold protein that recruits the DNA polymerase and DNA ligase required for filling and sealing the damaged strand. XRCC1 can also recruit end-processing enzymes, such as PNK (polynucleotide kinase 3'-phosphatase), Aprataxin and APLF (aprataxin/PNK-like factor), which ensure the availability of a free 3'-hydroxyl on one side of the gap, and a 5'-phosphate group on the other, for the polymerase and ligase reactions respectively. PNK binds to a phosphorylated segment of XRCC1 (between its two C-terminal BRCT domains) via its Forkhead-associated (FHA) domain. We show here, contrary to previous studies, that the FHA domain of PNK binds specifically, and with high affinity to a multiply phosphorylated motif in XRCC1 containing a pSer-pThr dipeptide, and forms a 2:1 PNK:XRCC1 complex. The high-resolution crystal structure of a PNK-FHA-XRCC1 phosphopeptide complex reveals the basis for this unusual bis-phosphopeptide recognition, which is probably a common feature of the known XRCC1-associating end-processing enzymes

Social referencing and social appraisal: commentary on the Clément and Dukes (2016) and Walle et al. (2016) articles

We comment on two articles on social referencing and social appraisal. We agree with Walle, Reschke, and Knothe’s (2017) argument that at one level of analysis, social referencing and social appraisal are functionally equivalent: In both cases, another person’s emotional expression is observed and this expression informs the observer’s own emotional reactions and behavior. However, we also agree with Clément and Dukes’s (2017) view that (at another level of analysis), there is an important difference between social referencing and social appraisal. We also argue that they are likely to occur at different stages of emotion process

Premi Asuransi Jiwa Berjangka Naik Dengan Menggunakan Hukum De Moivre

This article discusses the premium for participants whose age are years old, who participate in increasing term life insurance program. Premium calculated are a single premium, the annual premium, and the premium with times payment a year. The premiums consist of a single net premium calculation, the annual net premium, and net premium payments with times in a year that are influenced by due life annuity and management expense insurance. Premium calculation used in this article of actuarialassumptions is the De Moivre of law

Quality engineering of a traction alternator by robust design

Robust design is an engineering methodology for improving productivity during research and development so that high-quality products can be developed and produced quickly and at low cost. A large electrical company was developing traction alternators for a diesel electrical engine. Customer requirement was to obtain very high efficiency which, in turn, was influenced by several design parameters. The usual approach of the 'design-build-test' cycle was considered time-consuming and costly; it used to take anywhere from 4 months to 1 year before finalizing the product design parameters as it involved physical assembly and also testing. Instead, the authors used Taguchi's parameter design approach. This approach took about 8 weeks to arrive at optimum design parameter values; clearly demonstrating the cutting edge of this methodology over the traditional design-build-test approach. The prototype built and tested accordingly gave satisfactory overall performance, meeting and even exceeding customer requirements

P Wave Meson Spectrum in a Relativistic Model with Instanton Induced Interaction

On the basis of the phenomenological relativistic harmonic models for quarks we have obtained the masses of P wave mesons. The full Hamiltonian used in the investigation has Lorentz scalar + vector confinement potential, along with one gluon exchange potential (OGEP) and the instanton-induced quark-antiquark interaction (III). A good agreement is obtained with the experimental masses. The respective role of III and OGEP for the determination of the meson masses is discussed.Comment: Corrected typo