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1.
In eukaryotic cells, cyclin-dependent kinases (CDKs) have an important involvement at various points in the cell cycle. At the onset of S phase, active CDK is essential for chromosomal DNA replication, although its precise role is unknown. In budding yeast (Saccharomyces cerevisiae), the replication protein Sld2 (ref. 2) is an essential CDK substrate, but its phospho-mimetic form (Sld2-11D) alone neither affects cell growth nor promotes DNA replication in the absence of CDK activity, suggesting that other essential CDK substrates promote DNA replication. Here we show that both an allele of CDC45 (JET1) and high-copy DPB11, in combination with Sld2-11D, separately confer CDK-independent DNA replication. Although Cdc45 is not an essential CDK substrate, CDK-dependent phosphorylation of Sld3, which associates with Cdc45 (ref. 5), is essential and generates a binding site for Dpb11. Both the JET1 mutation and high-copy DPB11 by-pass the requirement for Sld3 phosphorylation in DNA replication. Because phosphorylated Sld2 binds to the carboxy-terminal pair of BRCT domains in Dpb11 (ref. 4), we propose that Dpb11 connects phosphorylated Sld2 and Sld3 to facilitate interactions between replication proteins, such as Cdc45 and GINS. Our results demonstrate that CDKs regulate interactions between BRCT-domain-containing replication proteins and other phosphorylated proteins for the initiation of chromosomal DNA replication; similar regulation may take place in higher eukaryotes. 相似文献
2.
Roberts AE Araki T Swanson KD Montgomery KT Schiripo TA Joshi VA Li L Yassin Y Tamburino AM Neel BG Kucherlapati RS 《Nature genetics》2007,39(1):70-74
Noonan syndrome, the most common single-gene cause of congenital heart disease, is characterized by short stature, characteristic facies, learning problems and leukemia predisposition. Gain-of-function mutations in PTPN11, encoding the tyrosine phosphatase SHP2, cause approximately 50% of Noonan syndrome cases. SHP2 is required for RAS-ERK MAP kinase (MAPK) cascade activation, and Noonan syndrome mutants enhance ERK activation ex vivo and in mice. KRAS mutations account for <5% of cases of Noonan syndrome, but the gene(s) responsible for the remainder are unknown. We identified missense mutations in SOS1, which encodes an essential RAS guanine nucleotide-exchange factor (RAS-GEF), in approximately 20% of cases of Noonan syndrome without PTPN11 mutation. The prevalence of specific cardiac defects differs in SOS1 mutation-associated Noonan syndrome. Noonan syndrome-associated SOS1 mutations are hypermorphs encoding products that enhance RAS and ERK activation. Our results identify SOS1 mutants as a major cause of Noonan syndrome, representing the first example of activating GEF mutations associated with human disease and providing new insights into RAS-GEF regulation. 相似文献
3.
目的是将用于测量片状试样的热扩散率的激光闪光法推广至测量薄膜试样。应用 1 5纳秒脉冲 Nd:YAG激光及响应时间 0 .9微秒的 (Hg,Cd) Te红外探测器等建立了闪光法热扩散率测量系统 ,并应用此系统对微米量级厚度的不锈钢薄膜进行了测量。同时针对将激光闪光法应用于薄膜时所出现的问题 ,如激光的有限脉冲时间及有限吸收厚度效应 ,测量系统的滞后效应 ,以及增强红外吸收及辐射用表面黑化膜的影响进行了分析并提出了解决方法 相似文献
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<正> This paper analyzes performance of optimal channel estimation and multiuser detection(MUD) in a block-fading code-division multiple-access (CDMA) channel on the assumptions of randomspreading and large-system limit,by using the replica method developed in statistical mechanics.The authors find that the asymptotic spectral efficiency of the linear minimum mean-squared error(LMMSE) MUD which was proposed and analyzed by Evans and Tse in 2000 is indistinguishable fromthat of the optimal MUD for small system loads.Our results imply that performance of MUD scarcelyimproves even if one spends more computational cost than that of the LMMSE MUD,i.e.,at most thecube of the number of users,on the above-described conditions. 相似文献
6.
In the research field of proton exchange membrane fuel cells, the design of electrocatalytic
activities on Pt-oxide promoter in the anode side has attracted attention for improvement
of CO tolerance of Pt in anode side and a lowering of large over-potential loss of the oxygen
reduction reaction on the cathode in the fuel cells. In the Pt-oxide promoter series, Pt–CeOx/C is
one of the unique systems. It is because the unique behavior of CeOx such as electrochemical redox
reaction between Ce3t and Ce4t in the anodic and cathodic reactions of fuel cell is observed. The
present short review gives an overview of the recent works for improvement of the CO tolerance of
Pt in the Pt–CeOx/C anodes and enhancement of the oxygen reduction reaction activity on Pt in the
Pt–CeOx/C cathodes for fuel cell application. To show the design paradigm for fabrication of high
quality Pt–CeOx/C electrodes, the authors re-introduced parts of our research results to highlight
the important role of interface structure of Pt–CeOx based on the ultimate analysis results. The usefulness of the combined approach of microanalysis and the processing route design is
presented. 相似文献
7.
The grain boundary plays an important role in the electrical behaviors of solid oxide electrolytes for solid state fuel cells. To reveal the relationship between the structure and the ionic conductivity of grain boundary,the conductive properties of {1 1 1} and {1 1 0} twist grain boundaries in 8 mol% yttria-stabilized zirconia have been examined. These boundaries have a series of Σ values defined by the coincident site lattice model. It has been found that the activation energy of {1 1 1} twist grain boundary increases and then decreases with the Σ value,while that of the {1 1 0} boundary shows an opposite trend. It is suggested that the properties can reflect the balance of the effects of lattice mismatch on the diffusion ability of oxygen vacancies and the segregation of oxygen vacancies and Y3 tions. Therefore,the properties in polycrystalline electrolyte can be adjusted by controlling the grain boundary structures. 相似文献
8.
Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs. 总被引:37,自引:0,他引:37
H Meguro H Mori K Araki E Kushiya T Kutsuwada M Yamazaki T Kumanishi M Arakawa K Sakimura M Mishina 《Nature》1992,357(6373):70-74
The glutamate receptor (GluR) channel plays a key part in brain function. Among GluR channel subtypes, the NMDA (N-methyl-D-aspartate) receptor channel which is highly permeable to Ca2+ is essential for the synaptic plasticity underlying memory, learning and development. Furthermore, abnormal activation of the NMDA receptor channel may trigger the neuronal cell death observed in various brain disorders. A complementary DNA encoding a subunit of the rodent NMDA receptor channel (NMDAR1 or zeta 1) has been cloned and its functional properties investigated. Here we report the identification and primary structure of a novel mouse NMDA receptor channel subunit, designated as epsilon 1, after cloning and sequencing the cDNA. The epsilon 1 subunit shows 11-18% amino-acid sequence identity with rodent GluR channel subunits that have been characterized so far and has structural features common to neurotransmitter-gated ion channels. Expression from cloned cDNAs of the epsilon 1 subunit together with the zeta 1 subunit in Xenopus oocytes yields functional GluR channels with high activity and characteristics of the NMDA receptor channel. Furthermore, the heteromeric NMDA receptor channel can be activated by glycine alone. 相似文献
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