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1.
Sensors (Basel) ; 22(9)2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35591053

RESUMO

The study investigates the effect of changing various input parameters on the pressure responses at acoustic cavities of a droplet-based acoustic printing device consisting of a Fabry-Pérot (FP) resonator and a standing wave-source chamber. The standing wave of the acoustic radiation pressure at the FP resonator is analyzed. The behavior of the standing wave and acoustic radiation force at the FP resonator is presented and compared with the measured results by varying the position of the standing wave-generating plate. The pressure changes inside the standing wave-source chamber are investigated and discussed to determine the reason for the sudden high-pressure drop at the FP resonator. Furthermore, the effects of inserting the nozzle and droplet inside the FP resonator on the standing wave and acoustic radiation force are analyzed. Experimental analysis is performed by collecting acoustic pressure data at the outlet of the FP resonator. The simulated and measured pressure drop behaviors are compared. The presented numerical approach can be used to set optimal design guidelines for obtaining a higher acoustic pressure inside the acoustic cavities of droplet-based acoustic jetting and other acoustofluidic devices.

2.
Sci Rep ; 12(1): 1485, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-35087151

RESUMO

The development of a new ultrasonic transducer capable of improved focusing performance has become a necessity to overcome the limitations of conventional ultrasonic transducer technology. In this study, we designed and optimized a metasurface piezoelectric ring device, and using multiphysics finite element analysis, we examined the performance of a planar ultrasonic transducer consisting of this device, a matching layer, a backing layer, and housing in producing a needle-like subwavelength focusing beam in water. For practical experiments, a metasurface piezoelectric ring device was fabricated using a laser ablation process. Subsequently, using a pulse-echo test, we found that the - 6 dB bandwidth of a planar ultrasonic transducer with a center frequency of 1.0 MHz was 37.5%. In addition, the results of an ultrasonic-focusing performance test showed that the full width at half-maximum of the axial subwavelength focusing beam was 0.78λ, and the full lateral width at half-maximum of the subwavelength lateral focusing beam was 7.03λ at a distance of 10.89λ. The needle-like focused ultrasonic beam technology implemented with a piezoelectric ring array based new planar ultrasound transducer is expected to be used in high-resolution imaging devices or medical ultrasound focusing devices in the future.

3.
Polymers (Basel) ; 13(21)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34771189

RESUMO

Divinylsiloxane-bis-benzocyclobutene (DVS-BCB) has attracted significant attention as an intermediate bonding material, owing to its excellent properties. However, its applications are limited, due to damage to peripheral devices at high curing temperatures and unoptimized compressive pressure. Therefore, it is necessary to explore the compressive pressure condition for DVS-BCB bonding. This study demonstrates an optimization process for void-free DVS-BCB bonding. The process for obtaining void-free DVS-BCB bonding is a vacuum condition of 0.03 Torr, compressive pressure of 0.6 N/mm2, and curing temperature of 250 °C for 1 h. Herein, we define two factors affecting the DVS-BCB bonding quality through the DVS-BCB bonding mechanism. For strong DVS-BCB bonding, void-free and high-density chemical bonds are required. Therefore, we observed the DVS-BCB bonding under various compressive pressure conditions at a relatively low temperature (250 °C). The presence of voids and high-density crosslinking density was examined through near-infrared confocal laser microscopy and Fourier-transform infrared microscopy. We also evaluated the adhesion of the DVS-BCB bonding, using a universal testing machine. The results suggest that the good adhesion with no voids and high crosslinking density was obtained at the compressive pressure condition of 0.6 N/mm2. We believe that the proposed process will be of great significance for applications in semiconductor and device packaging technologies.

4.
Front Bioeng Biotechnol ; 9: 693849, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336805

RESUMO

Cochlear implants (CIs) have become the standard treatment for severe-to-profound sensorineural hearing loss. Conventional CIs have some challenges, such as the use of extracorporeal devices, and high power consumption for frequency analysis. To overcome these, artificial basilar membranes (ABMs) made of piezoelectric materials have been studied. This study aimed to verify the conceptual idea of a totally implantable ABM system. A prototype of the totally implantable system composed of the ABM developed in previous research, an electronic module (EM) for the amplification of electrical output from the ABM, and electrode was developed. We investigated the feasibility of the ABM system and obtained meaningful auditory brainstem responses of deafened guinea pigs by implanting the electrode of the ABM system. Also, an optimal method of coupling the ABM system to the human ossicle for transducing sound waves into electrical signals using the middle ear vibration was studied and the electrical signal output according to the sound stimuli was measured successfully. Although the overall power output from the ABM system is still less than the conventional CIs and further improvements to the ABM system are needed, we found a possibility of the developed ABM system as a totally implantable CIs in the future.

5.
Nanomaterials (Basel) ; 10(12)2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33317076

RESUMO

Flexible electrodes should have a good mechanical durability and electrical properties under even extreme bending and deformation conditions. We fabricated such an electrode using an inkjet printing system. In addition, annealing was perfo3rmed under curing temperatures of 150, 170, and 190 °C to improve the electrical resistance performance of the electrode. Scanning electron microscopy, X-ray diffraction, nanoindentation, and surface profile measurements were performed to measure and analyze the electrode characteristics and the change in the shape of the coffee ring. The bending deformation behavior of the electrode was predicted by simulations. To confirm the bending durability of the flexible electrode according to different curing temperatures, the bending deformation and electrical resistance were simultaneously tested. It was found that the electrode cured at a temperature of 170 °C could endure 20,185 bending cycles and had the best durability, which was consistent with the predicted simulation results. Moreover, the average specific resistance before the electrode was disconnected was 13.45 µΩ cm, which is similar to the conventional electrode value. These results are expected to increase the durability and life of flexible electrodes, which can be used in flexible electronic devices, sensors, and wearable devices that are subjected to significant bending deformation.

6.
Micromachines (Basel) ; 11(10)2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003298

RESUMO

After a piezoelectric inkjet printhead jets the first droplet, the actuating membrane still vibrates, creating residual vibrations in the ink channel, which can degrade the inkjet printhead performance. For suppressing these vibrations, an optimized actuating voltage waveform with two pulses must be obtained, of which the first pulse is used for jetting and the second pulse is used to suppress the residual vibrations. In this study, the pressure history within the ink channel of a recirculating piezoelectric inkjet printhead was first acquired using lumped element modeling. Then, for suppressing residual vibrations, a bipolar voltage waveform was optimized via analysis of the tuning time (tt), dwell time (td2), rising time (tr2), falling time (tf2), and voltage amplitude of the second pulse. Two voltage waveforms, Waveform 01 and Waveform 02, were optimized thereafter. In Waveform 01, tt=2 µs, td2=2 µs, and tr2 and tf2=1 µswere finalized as the optimal parameters; in the case of another waveform, the optimal parameters of td2, tr2, and tf2 were found to be 4, 1, and 1 µs, respectively. The optimal voltage amplitude of the second pulse was found to be 1/3 the amplitude of the first pulse. On the basis of our analysis, the tuning time in Waveform 01 is the most sensitive parameter, and the performance yielded is even poorer than that yielded by standard waveform, if not optimized. Therefore, the other waveform is recommended for the suppression of residual vibrations.

7.
Sci Rep ; 10(1): 10769, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32612240

RESUMO

During our research, we explored a novel way to represent subwavelength imaging and derived a transmission equation to explicate the FP (Fabry-Pérot) resonance phenomena. Subsequently, using analysis and observation, we performed deep-subwavelength imaging. Both numerically and experimentally, imaging with super-resolution was achieved at deep subwavelength scale of λ/56.53 with a lens thickness 212 mm. Our results also showed that by increasing lens thickness, higher resolution can be achieved. Moreover, via a single source study, we showed the full width at half maximum range and predicted the size of smallest detectable object. We also observed that with a greater lens thickness, finer features could be detected. These findings may open a new route in near-field imaging for practical applications such as biometric sensors, ultrasonic medical equipment, and non-destructive testing.

8.
Micromachines (Basel) ; 10(11)2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31698843

RESUMO

The recirculation of ink in an inkjet printhead system keeps the ink temperature and viscosity constant, and leads to the development of a high-performance device. Herein, we propose a recirculating piezo-driven micro-electro-mechanical system (MEMS)-based inkjet printhead that has a pressure chamber, a nozzle, and double restrictors. The design and characteristic analysis are performed using a two-port lumped element model (LEM) to investigate the effect of design parameters on the system responses. Using LEM, the jetting pressure at the pressure chamber, velocity at the nozzle inlet, meniscus pressure, and Helmholtz resonance frequency are predicted and the comparative analysis of the jetting pressure and velocity between LEM and the finite element method (FEM) simulation is conducted to validate our proposed LEM method. Furthermore, the effect of a change in major design parameters on the jetting pressure, velocity, and Helmholtz resonance frequency is analyzed. On the basis of this analysis, the optimized device dimensions are finalized. From our analysis, it is also concluded that the restrictor is more sensitive than the pressure chamber in terms of their variations in depth. As the cross-talk effect can occur due to an array of hundreds or thousands of nozzles, we investigated the effect of a single activated nozzle on the non-activated neighboring nozzles, as well as the effect of multi-activated nozzles on a single central nozzle using our proposed LEM.

9.
Sci Rep ; 8(1): 15535, 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30341393

RESUMO

We report new frequency bands for subwavelength imaging by using the resonant tunneling method which have not been explored previously. As per the existing theory of resonant tunneling, imaging frequency is limited for a certain number of crystals. However, after conducting an analytical analysis over a wide range of frequencies, we observed that higher frequencies do exist for subwavelength imaging. We verified this observation both numerically and experimentally. We extended our study to observe the effect of lattice periodicity on image resolution. By reducing periodicity during experiment, we achieved a resolution of λ/9.5 at the conventional region and λ/2.45 at the higher band region.

10.
Oncotarget ; 8(70): 115041-115053, 2017 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-29383140

RESUMO

The INO80 chromatin-remodeling complex performs functions in many chromosomal processes that are crucial for genome stability, such as DNA replication and stalled replication fork recovery. Although these functions suggest that INO80 acts as a tumor suppressor, its specific role in tumorigenesis has remained obscure. Here, we show that a haploinsufficient mutation of Ino80, the catalytic ATPase of the INO80 complex, decreased intestinal adenomatous polyps and increased survival in an Apcmin/+ mouse model of colon cancer. Experiments using tumors obtained from Apcmin/+ mice and cells from human colon cancers showed that this Ino80 defect induced stalled replication forks, the concomitant activation of ATR-Chk1 signaling and an increase in apoptosis, suggesting that Ino80 haploinsufficiency inhibited colon cancer tumorigenesis by activating replication stress-induced ATR-Chk1 signaling to increase apoptosis. Importantly, in human colon cancer, we observed that the INO80 subunits were frequently present in high copy numbers and exhibited a high rate of amplification and increased protein expression. These results show that in contrast to our original prediction that INO80 acts as a tumor suppressor, INO80 actually functions oncogenically to promote colon tumorigenesis. INO80 therefore represents a novel therapeutic target in colon cancer. The results of this study also reinforce the emerging notion that while genomic instability can promote tumorigenesis, in certain genetic contexts, it can also act as a tumor suppressor.

11.
Sci Rep ; 6: 32300, 2016 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-27562634

RESUMO

Artificially designed acoustic meta-surfaces have the ability to manipulate sound energy to an extraordinary extent. Here, we report on a new type of directional reflective surface consisting of an array of sub-wavelength Helmholtz resonators with varying internal coiled path lengths, which induce a reflection phase gradient along a planar acoustic meta-surface. The acoustically reshaped reflective surface created by the gradient-impeding meta-surface yields a distinct focal line similar to a parabolic cylinder antenna, and is used for directive sound beamforming. Focused beam steering can be also obtained by repositioning the source (or receiver) off axis, i.e., displaced from the focal line. Besides flat reflective surfaces, complex surfaces such as convex or conformal shapes may be used for sound beamforming, thus facilitating easy application in sound reinforcement systems. Therefore, directional reflective surfaces have promising applications in fields such as acoustic imaging, sonic weaponry, and underwater communication.


Assuntos
Acústica/instrumentação , Localização de Som , Espectrografia do Som/instrumentação , Som , Estimulação Acústica , Algoritmos , Humanos , Modelos Teóricos , Processamento de Sinais Assistido por Computador , Espectrografia do Som/métodos
12.
Sensors (Basel) ; 15(8): 18851-64, 2015 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-26263995

RESUMO

This paper presents the development of a piezoelectric artificial cochlea (PAC) device capable of analyzing vibratory signal inputs and converting them into electrical signal outputs without an external power source by mimicking the function of human cochlea within an audible frequency range. The PAC consists of an artificial basilar membrane (ABM) part and an implantable packaged part. The packaged part provides a liquid environment through which incoming vibrations are transmitted to the membrane part. The membrane part responds to the transmitted signal, and the local area of the ABM part vibrates differently depending on its local resonant frequency. The membrane was designed to have a logarithmically varying width from 0.97 mm to 8.0 mm along the 28 mm length. By incorporating a micro-actuator in an experimental platform for the package part that mimics the function of a stapes bone in the middle ear, we created a similar experimental environment to cochlea where the human basilar membrane vibrates. The mechanical and electrical responses of fabricated PAC were measured with a laser Doppler vibrometer and a data acquisition system, and were compared with simulation results. Finally, the fabricated PAC in a biocompatible package was developed and its mechanical and electrical characteristics were measured. The experimental results shows successful frequency separation of incoming mechanical signal from micro-actuator into frequency bandwidth within the 0.4 kHz-5 kHz range.


Assuntos
Materiais Biocompatíveis/química , Implantes Cocleares , Eletricidade , Fenômenos Mecânicos , Embalagem de Produtos , Desenho de Prótese , Análise de Elementos Finitos , Humanos , Processamento de Sinais Assistido por Computador , Vibração
13.
Sci Rep ; 4: 7421, 2014 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-25502279

RESUMO

The inherent attenuation of a homogeneous viscous medium limits radiation propagation, thereby restricting the use of many high-frequency acoustic devices to only short-range applications. Here, we design and experimentally demonstrate an acoustic metamaterial localization cavity which is used for sound pressure level (SPL) gain using double coiled up space like structures thereby increasing the range of detection. This unique behavior occurs within a subwavelength cavity that is 1/10(th) of the wavelength of the incident acoustic wave, which provides up to a 13 dB SPL gain. We show that the amplification results from the Fabry-Perot resonance of the cavity, which has a simultaneously high effective refractive index and effective impedance. We also experimentally verify the SPL amplification in an underwater environment at higher frequencies using a sample with an identical unit cell size. The versatile scalability of the design shows promising applications in many areas, especially in acoustic imaging and underwater communication.

14.
Nat Commun ; 5: 5128, 2014 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-25283999

RESUMO

The INO80 chromatin-remodelling complex has been implicated in DNA replication during stress in yeast. However, its role in normal DNA replication and its underlying mechanisms remain unclear. Here, we show that INO80 binds to replication forks and promotes fork progression in human cells under unperturbed, normal conditions. We find that Ino80, which encodes the catalytic ATPase of INO80, is essential for mouse embryonic DNA replication and development. Ino80 is recruited to replication forks through interaction with ubiquitinated H2A--aided by BRCA1-associated protein-1 (BAP1), a tumour suppressor and nuclear de-ubiquitinating enzyme that also functions to stabilize Ino80. Importantly, Ino80 is downregulated in BAP1-defective cancer cells due to the lack of an Ino80 stabilization mechanism via BAP1. Our results establish a role for INO80 in normal DNA replication and uncover a mechanism by which this remodeler is targeted to replication forks, suggesting a molecular basis for the tumour-suppressing function of BAP1.


Assuntos
Adenosina Trifosfatases/metabolismo , DNA Helicases/metabolismo , Replicação do DNA , Neoplasias/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/metabolismo , ATPases Associadas a Diversas Atividades Celulares , Animais , Proteínas de Ligação a DNA , Regulação para Baixo , Éxons , Feminino , Regulação Neoplásica da Expressão Gênica , Genótipo , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Confocal , Ligação Proteica , RNA Interferente Pequeno/metabolismo , Transfecção , Técnicas do Sistema de Duplo-Híbrido , Ubiquitina/química
15.
Sci Rep ; 4: 4165, 2014 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-24584552

RESUMO

The emission enhancement of sound without electronic components has wide applications in a variety of remote systems, especially when highly miniaturized (smaller than wavelength) structures can be used. The recent advent of acoustic metamaterials has made it possible to realize this. In this study, we propose, design, and demonstrate a new class of acoustic cavity using a double-walled metamaterial structure operating at an extremely low frequency. Periodic zigzag elements which exhibit Fabry-Perot resonant behavior below the phononic band-gap are used to yield strong sound localization within the subwavelength gap, thus providing highly effective emission enhancement. We show, both theoretically and experimentally, 10 dB sound emission enhancement near 1060 Hz that corresponds to a wavelength approximately 30 times that of the periodicity. We also provide a general guideline for the independent tuning of the quality factor and effective volume of acoustic metamaterials. This approach shows the flexibility of our design in the efficient control of the enhancement rate.

16.
Sensors (Basel) ; 14(1): 117-28, 2013 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-24361926

RESUMO

In this research, we have developed a multi-channel piezoelectric acoustic sensor (McPAS) that mimics the function of the natural basilar membrane capable of separating incoming acoustic signals mechanically by their frequency and generating corresponding electrical signals. The McPAS operates without an external energy source and signal processing unit with a vibrating piezoelectric thin film membrane. The shape of the vibrating membrane was chosen to be trapezoidal such that different locations of membrane have different local resonance frequencies. The length of the membrane is 28 mm and the width of the membrane varies from 1 mm to 8 mm. Multiphysics finite element analysis (FEA) was carried out to predict and design the mechanical behaviors and piezoelectric response of the McPAS model. The designed McPAS was fabricated with a MEMS fabrication process based on the simulated results. The fabricated device was tested with a mouth simulator to measure its mechanical and piezoelectrical frequency response with a laser Doppler vibrometer and acoustic signal analyzer. The experimental results show that the as fabricated McPAS can successfully separate incoming acoustic signals within the 2.5 kHz-13.5 kHz range and the maximum electrical signal output upon acoustic signal input of 94 dBSPL was 6.33 mVpp. The performance of the fabricated McPAS coincided well with the designed parameters.


Assuntos
Acústica/instrumentação , Membrana Basilar , Membranas Artificiais , Modelos Teóricos
17.
Biochem Biophys Res Commun ; 416(3-4): 416-20, 2011 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-22133677

RESUMO

The human INO80 chromatin remodeling complex, comprising the Ino80 ATPase (hIno80) and the associated proteins such as Tip49a, has been implicated in a variety of nuclear processes other than transcription. We previously have found that hIno80 interacts with tubulin and co-localizes with the mitotic spindle and is required for spindle formation. To better understand the role of hIno80 in spindle formation, we further investigated the interaction between hIno80 and microtubule. Here, we show that the N-terminal domain, dispensable for the nucleosome remodeling activity, is important for hIno80 to interact with tubulin and co-localize with the spindle. The hIno80 N-terminal domain binds to monomeric tubulin and polymerized microtubule in vitro, and the E-hook of tubulin, involved in the polymerization of microtubule, is critical for this binding. Tip49a, which has been reported to associate with the spindle, does not bind to microtubule in vitro and dispensable for spindle formation in vivo. These results suggest that hIno80 can play a direct role in the spindle assembly independent of its chromatin remodeling activity.


Assuntos
DNA Helicases/metabolismo , Microtúbulos/metabolismo , Fuso Acromático/metabolismo , Tubulina (Proteína)/metabolismo , ATPases Associadas a Diversas Atividades Celulares , Montagem e Desmontagem da Cromatina , DNA Helicases/genética , Proteínas de Ligação a DNA , Células HEK293 , Humanos , Conformação Proteica , Deleção de Sequência , Tubulina (Proteína)/química
18.
Biochem J ; 431(2): 179-87, 2010 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-20687897

RESUMO

Recent studies have shown that the SWI/SNF family of ATP-dependent chromatin-remodelling complexes play important roles in DNA repair as well as in transcription. The INO80 complex, the most recently described member of this family, has been shown in yeast to play direct role in DNA DSB (double-strand break) repair without affecting the expression of the genes involved in this process. However, whether this function of the INO80 complex is conserved in higher eukaryotes has not been investigated. In the present study, we found that knockdown of hINO80 (human INO80) confers DNA-damage hypersensitivity and inefficient DSB repair. Microarray analysis and other experiments have identified the Rad54B and XRCC3 (X-ray repair complementing defective repair in Chinese-hamster cells 3) genes, implicated in DSB repair, to be repressed by hINO80 deficiency. Chromatin immunoprecipitation studies have shown that hINO80 binds to the promoters of the Rad54B and XRCC3 genes. Re-expression of the Rad54B and XRCC3 genes rescues the DSB repair defect in hINO80-deficient cells. These results suggest that hINO80 assists DSB repair by positively regulating the expression of the Rad54B and XRCC3 genes. Therefore, unlike yeast INO80, hINO80 can contribute to DSB repair indirectly via gene expression, suggesting that the mechanistic role of this chromatin remodeller in DSB repair is evolutionarily diversified.


Assuntos
Montagem e Desmontagem da Cromatina/genética , Quebras de DNA de Cadeia Dupla , DNA Helicases/genética , DNA Helicases/metabolismo , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Proteínas Nucleares/genética , ATPases Associadas a Diversas Atividades Celulares , DNA Helicases/deficiência , Técnicas de Silenciamento de Genes , Células HeLa , Histonas/metabolismo , Humanos , Regiões Promotoras Genéticas/genética , Ligação Proteica
19.
Cell Mol Life Sci ; 67(13): 2283-96, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20237820

RESUMO

Although INO80 chromatin remodeling enzyme has been shown in yeast to play roles in non-transcriptional nuclear processes such as DNA replication, its cellular functions in higher eukaryotes have remained largely unexplored. Here, we provide evidence that human INO80 (hINO80) participates in both DNA replication and chromosome segregation during the normal cell division cycle. hINO80 binds to chromatin localizing at replication forks during the S-phase, and is required for efficient DNA synthesis and S-phase progression. Unexpectedly, hINO80 associates with spindle microtubule during mitosis, and its deficiency leads to defective microtubule assembly and abnormal chromosome segregation. Consistent with these results, hINO80 is critical for suppressing aneuploidy and structural chromosome abnormalities. This work therefore not only emphasizes the evolutionary importance of INO80 in DNA replication but also reveals a new role for this remodeler in chromosome segregation, both of which likely come into play in maintaining the genome integrity.


Assuntos
Cromatina/metabolismo , Segregação de Cromossomos , DNA Helicases/fisiologia , Replicação do DNA , Instabilidade Genômica , ATPases Associadas a Diversas Atividades Celulares , Aneuploidia , Montagem e Desmontagem da Cromatina , DNA Helicases/metabolismo , Proteínas de Ligação a DNA , Células HeLa , Humanos , Mitose , Fase S
20.
DNA Repair (Amst) ; 8(1): 29-39, 2009 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-18822392

RESUMO

Although SWI/SNF chromatin remodeling complexes play important roles in transcription, recent studies suggest that they also participate directly in DNA repair. In yeast, SWI/SNF and related RSC complexes have been shown to be recruited to the sites of DNA double strand breaks (DSBs) to facilitate DNA repair. We recently have shown that mammalian SWI/SNF complexes contribute to DBS repair by direct mechanisms of stimulating the phosphorylation of histone H2AX at DSB-surrounding chromatin. Here we investigated the role of mammalian SWI/SNF complexes in cell survival after DNA damage. When SWI/SNF was inactivated by means of dominant negativity or its catalytic subunit BRG1 was knockdowned by small interfering RNA, cells became highly susceptible to DNA damage-induced apoptosis. SWI/SNF inactivation had no effect on the activation and establishment of G2/M DNA damage checkpoint. However, SWI/SNF-defective cells could not sustain the G2/M checkpoint long enough to survive DNA damage, and rather underwent apoptosis before entering mitosis. We also found that, although the basal state and DNA damage-triggered activation of p53 were normal, the kinetics of p53 downregulation was significantly delayed in SWI/SNF-defective cells. Finally, the sustained p53 activation in SWI/SNF-defective cells was accompanied by accumulation of unrepaired DSBs owing to inefficient DNA repair. These results suggest that mammalian SWI/SNF complexes prevent DNA damage-induced apoptosis in part by facilitating efficient repair and thereby ensuring timely elimination of unrepaired DSBs that could otherwise lead to excessive prolongation of p53 activation.


Assuntos
Apoptose , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Dano ao DNA , Fatores de Transcrição/metabolismo , Proteínas de Ciclo Celular/metabolismo , Morte Celular , Divisão Celular , Linhagem Celular , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Fase G2 , Humanos , Proteína Supressora de Tumor p53/metabolismo
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