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1.
J Biol Chem ; 297(4): 101148, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34473993

RESUMO

The proper cellular response to DNA double-strand breaks (DSBs) is critical for maintaining the integrity of the genome. RecQL4, a DNA helicase of which mutations are associated with Rothmund-Thomson syndrome (RTS), is required for the DNA DSB response. However, the mechanism by which RecQL4 performs these essential roles in the DSB response remains unknown. Here, we show that RecQL4 and its helicase activity are required for maintaining the stability of the Mre11-Rad50-Nbs1 (MRN) complex on DSB sites during a DSB response. We found using immunocytochemistry and live-cell imaging that the MRN complex is prematurely disassembled from DSB sites in a manner dependent upon Skp2-mediated ubiquitination of Nbs1 in RecQL4-defective cells. This early disassembly of the MRN complex could be prevented by altering the ubiquitination site of Nbs1 or by expressing a deubiquitinase, Usp28, which sufficiently restored homologous recombination repair and ATM, a major checkpoint kinase against DNA DSBs, activation abilities in RTS, and RecQL4-depleted cells. These results suggest that the essential role of RecQL4 in the DSB response is to maintain the stability of the MRN complex on DSB sites and that defects in the DSB response in cells of patients with RTS can be recovered by controlling the stability of the MRN complex.


Assuntos
Hidrolases Anidrido Ácido/metabolismo , Proteínas de Ciclo Celular/metabolismo , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Proteínas de Ligação a DNA/metabolismo , Proteína Homóloga a MRE11/metabolismo , Complexos Multiproteicos/metabolismo , Proteínas Nucleares/metabolismo , RecQ Helicases/metabolismo , Hidrolases Anidrido Ácido/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Células HEK293 , Humanos , Proteína Homóloga a MRE11/genética , Complexos Multiproteicos/genética , Proteínas Nucleares/genética , RecQ Helicases/genética
2.
Nat Commun ; 12(1): 2714, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976126

RESUMO

Durability of high-energy throughput batteries is a prerequisite for electric vehicles to penetrate the market. Despite remarkable progresses in silicon anodes with high energy densities, rapid capacity fading of full cells with silicon-graphite anodes limits their use. In this work, we unveil degradation mechanisms such as Li+ crosstalk between silicon and graphite, consequent Li+ accumulation in silicon, and capacity depression of graphite due to silicon expansion. The active material properties, i.e. silicon particle size and graphite hardness, are then modified based on these results to reduce Li+ accumulation in silicon and the subsequent degradation of the active materials in the anode. Finally, the cycling performance is tailored by designing electrodes to regulate Li+ crosstalk. The resultant full cell with an areal capacity of 6 mAh cm-2 has a cycle life of >750 cycles the volumetric energy density of 800 Wh L-1 in a commercial cell format.

3.
ACS Appl Mater Interfaces ; 10(3): 2414-2422, 2018 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-29278323

RESUMO

Eutectic mixtures of alkali nitrates are known to increase the sorption capacity and kinetics of MgO-based sorbents. Underlying principles and mechanisms for CO2 capture on such sorbents have already been established; however, real-time observation of the system was not yet accomplished. In this work, we present the direct-observation of the CO2 capture phenomenon on a KNO3-LiNO3 eutectic mixture (EM)-promoted MgO sample, denoted as KLM, via in situ transmission electron microscopy (in situ TEM). Results revealed that the pseudoliquid EM undergoes structural rearrangement as MgCO3 evolves from the surface of MgO, resulting in surface roughening and evolution of cloudy structures that stay finely distributed after regeneration. From this, we propose a nucleation and structural rearrangement scheme for MgCO3 and EM, which involves the rearrangement of bulk EM to evenly distributed EM clusters due to MgCO3 saturation as adsorption proceeds. We also conducted studies on the interface between EM over solid MgO and MgCO3 formed during sorption, which further clarifies the interaction between MgO and EM. This study provides better insight into the sorption and regeneration mechanism, as well as the structural rearrangements involved in EM-promoted sorbents by basing not only on intrinsic evolutions but also on real-time observation of the system as a whole.

4.
J Nanosci Nanotechnol ; 11(7): 5633-9, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22121583

RESUMO

The thermal endurance and microstructural evolution of Ni-germanide (NiGe) and Pt-germanide (PtGe) on a Ge-on-Si substrate were compared in this paper. In case of the Ni/TiN structure, the sheet resistance exhibited a stable RTP window of 350 to 600 degrees C, while that of the Pt/TiN structure showed more stable characteristics up to 700 degrees C. Furthermore, after post-germanidation annealing, NiGe exhibited the formation of islands due to the severe agglomeration as well as a prominent grain boundary grooving, which accounts for the sharp increase of the sheet resistance from 550 degrees C, whereas PtGe showed a smooth and continuous surface morphological stability without signs of agglomeration even up to 600 degrees C. Although about two times higher resistivity (31.5 micro ohms-cm) and greater Ge consumption (3.27 nm) were shown, PtGe showed more stable sheet resistance, better surface and interface morphological stability and a wider thermal processing window above 100 degrees C than NiGe. Therefore, PtGe is more suitable for the germanided shallow source/drain for nano-scale Ge MOSFETs than NiGe.

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