• 제목/요약/키워드: H2AX

검색결과 122건 처리시간 0.029초

마우스 수정란에 있어서 부계 DNA 손상이 부계 DNA 퇴화 및 초기 배발달에 미치는 영향 (Effect of Paternal DNA Damage on Paternal DNA Degradation and Early Embryonic Development in Mouse Embryo: Supporting Evidence by GammaH2AX Expression)

  • 김창진;이경본
    • 한국동물생명공학회지
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    • 제34권3호
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    • pp.197-204
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    • 2019
  • This study was investigated to test whether the zygote recognized the topoisomerase II beta (TOP2B) mediated DNA fragmentation in epididymal spermatozoa or the nuclease degradation in vas deferens spermatozoa by testing for the presence of gammaH2AX (γH2AX). The γH2AX is phosphorylation of histone protein H2AX on serine 139 occurs at sites flanking DNA double-stranded breaks (DSBs). The presence of γH2AX in the pronuclei of mouse zygotes which were injected with DNA broke epididymal spermatozoa was tested by immunohistochemistry at 5 and 9 h post fertilization, respectively. Paternal pronuclei that arose from epididymal spermatozoa treated with divalent cations did not stain for γH2AX at 5 h. On the other hand, in embryos injected with vas deferences spermatozoa that had been treated with divalent cations, γH2AX was only present in paternal pronuclei, and not the maternal pronuclei at 5 h. Interestingly, both pronuclei stained positively for γH2AX for all treatments and controls at 9 h after sperm injection. In conclusion, the embryos recognize DNA that is damaged by nuclease, but not by TOP2B because H2AX in phosphorylated in paternal pronuclei resulting from spermatozoa treated with fragmented DNA from vas deferens spermatozoa treated with divalent cations, but not from epididymal spermatozoa treated the same way.

H2AX의 BRCA1 NLS domain과 BARD1 BRCT domain 각각과의 in vitro 상호 결합 (H2AX Directly Interacts with BRCA1 and BARD1 via its NLS and BRCT Domain Respectively in vitro)

  • 배승희;이선미;김수미;최태부;김차순;성기문;진영우;안성관
    • KSBB Journal
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    • 제24권4호
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    • pp.403-409
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    • 2009
  • 본 연구에서는 H2AX의 생리학적인 기능 및 분자세포 생물학적 기전 해석에 대한 보다 명확한 정보를 제시하고자, H2AX 관련 단백질들을 literature review 및 생물정보학적인 기술을 이용하여 최적의 결합 단백질체를 40개를 예측하곤 이들 가운데 상호작용 가능성이 높은 BRCA1와 BARD1 단백질을 선별하여 in vitro 결합실험을 통해 이를 증명하였다. 이들 두 가지의 유전자를 발굴하여, 클로닝하였다. 클로닝된 유전자를 이용하여 두 가지 단백질을 발현 및 정제하였으며, 단백질들의 자체적인 구조에 의한 결합능력을 판단하기 위해 in vitro binding assay법을 실시하였다. 단백질의 구조적 안정과 비특이적 결합을 억제하는 detergent만이 포함된 상태에서, 구조학적 및 물리학적 상호 결합의 유무를 판정할 수 있게 하였으며, BRCA1과 BARD1은 모두 H2AX에 결합함을 확인하였다. 이런 실험결과를 바탕으로 각각의 단백질에 대해 H2AX와의 최적 결합 부위를 알아내기 위해 각 유전자의 domain을 생물정보학적으로 분석하였다. 이에 RING domain, NES, NLS 및 BRCT domain에 해당하는 유전자 부분을 새로 클로닝하여, 다시 in vitro 결합실험 및 실험결과에 대한 literature review를 통한 분석을 실시한 결과, H2AX는 BRCA1의 NLS, BARD1의 BRCT domain 부분과 결합하는 것을 확인하였다. H2AX에 대한 BRCA1과 BARD1과의 결합은 DNA repair에 있어 BRCA1의 NLS와 BARD1의 BRCT domain을 통해 H2AX foci의 관련 세포 신호전달 기전에 중요한 역할을 하여 전체적으로 genomic stability에 영향을 미칠 가능성이 농후할 것으로 사료된다.

NORMAL INTERPOLATION ON AX=Y AND Ax=y IN A TRIDIAGONAL ALGEBRA $ALG\mathcal{L}$

  • Kang, Joo-Ho
    • Journal of applied mathematics & informatics
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    • 제24권1_2호
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    • pp.535-539
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    • 2007
  • Given operators X and Y acting on a separable complex Hilbert space $\mathcal{H}$, an interpolating operator is a bounded operator A such that AX=Y. In this article, we show the following: Let $Alg\mathcal{L}$ be a tridiagonal algebra on a separable complex Hilbert space $\mathcal{H}$ and let $X=(x_{ij})\;and\;Y=(y_{ij})$ be operators in $\mathcal{H}$. Then the following are equivalent: (1) There exists a normal operator $A=(a_{ij})\;in\;Alg\mathcal{L}$ such that AX=Y. (2) There is a bounded sequence $\{\alpha_n\}\;in\;\mathbb{C}$ such that $y_{ij}=\alpha_jx_{ij}\;for\;i,\;j\;{\in}\;\mathbb{N}$. Given vectors x and y in a separable complex Hilbert space $\mathcal{H}$, an interpolating operator is a bounded operator A such that Ax=y. We show the following: Let $Alg\mathcal{L}$ be a tridiagonal algebra on a separable complex Hilbert space $\mathcal{H}$ and let $x=(x_i)\;and\;y=(y_i)$ be vectors in $\mathcal{H}$. Then the following are equivalent: (1) There exists a normal operator $A=(a_{ij})\;in\;Alg\mathcal{L}$ such that Ax=y. (2) There is a bounded sequence $\{\alpha_n\}$ in $\mathbb{C}$ such that $y_i=\alpha_ix_i\;for\;i{\in}\mathbb{N}$.

Protective effects of Camellia sinensis fruit and fruit peels against oxidative DNA damage

  • Ahn, Joung-Jwa;Jang, Tae-Won;Park, Jae-Ho
    • Journal of Applied Biological Chemistry
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    • 제64권3호
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    • pp.237-244
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    • 2021
  • Camellia sinensis, Green tea, contains phenolic compounds that act to scavenge reactive oxygen species (ROS), such as catechin, epicatechin, etc. In contrast with the tea leaf, the bioactivity of its fruit and the fruit peels remains still unclear. This study focused on the effects of fruit and fruit peels of C. sinensis (FC and PC) against oxidative DNA damage in NIH/3T3 cells. The scavenging effects of FC and PC on ROS were assessed using 1,1-diphenyl-2-picryl hydrazyl or 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radicals. The measurement of ROS in cellular levels was conducted by DCFDA reagent and the protein expression of γ-H2AX, H2AX, cleaved caspase-3, p53, and, p-p53 was analyzed by immunoblotting. The gene expressions of p53 and H2AX were assessed using polymerase chain reaction techniques. The major metabolites of FC and PC were quantitatively measured analyzed and the amounts of phenolic compounds and flavonoids in PC were greater than those in FC. Further, PC suppressed ROS production, which protects the oxidative stress-induced DNA damage through reducing H2AX, p53, and caspase-3 phosphorylation. These results refer that the protective effects of FC and PC are mediated by inhibition of p53 signaling pathways, probably via the bioactivity of phenolic compounds. Thus, FC and PC can serve as a potential antioxidant in DNA damage-associated diseases.

BAF53 is Critical for Focus Formation of $\gamma$-H2AX in Response to DNA Damage

  • Park, Pan-Kyu;Kang, Dong-Hyun;Kwon, Hyock-Man
    • Animal cells and systems
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    • 제13권4호
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    • pp.405-409
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    • 2009
  • When DNA double-strand breaks (DSBs) were induced in mammalian cells, many DNA damage response proteins are accumulated at damage sites to form nuclear foci called IR-induced foci. Although the formation of foci has been shown to promote repair efficiency, the structural organization of chromatin in foci remains obscure. BAF53 is an actin-related protein which is required for maintenance of chromosome territory. In this study, we show that the formation of IR-induced foci by $\gamma$-H2AX and 53BP1 were reduced when BAF53 is depleted, while DSB- activated ATM pathway and the phosphorylation of H2AX remains intact after DNA damage in BAF53 knockdown cells. We also found that DSB repair efficiency was largely compromised in BAF53 knockdown cells. These results indicate that BAF53 is critical for formation of foci by $\gamma$-H2AX decorated chromatin at damage sites and the structural organization of chromatin in foci is an important factor to achieve the maximum efficiency of DNA repair.

INVERTIBLE INTERPOLATION ON AX = Y IN ALGL

  • Kang, Joo-Ho
    • 한국수학교육학회지시리즈B:순수및응용수학
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    • 제14권3호
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    • pp.161-166
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    • 2007
  • Given operators X and Y acting on a Hilbert space H, an interpolating operator is a bounded operator A such that AX = Y. An interpolating operator for n-operators satisfies the equation $AX_i=Y_i$, for i = 1,2,...,n. In this article, we showed the following: Let L, be a subspace lattice on a Hilbert space H and let X and Y be operators in B(H). Then the following are equivalent: (1) $$sup\{\frac{{\parallel}E^{\bot}Yf{\parallel}}{{\overline}{\parallel}E^{\bot}Xf{\parallel}}\;:\;f{\epsilon}H,\;E{\epsilon}L}\}\;<\;{\infty},\;sup\{\frac{{\parallel}Xf{\parallel}}{{\overline}{\parallel}Yf{\parallel}}\;:\;f{\epsilon}H\}\;<\;{\infty}$$ and $\bar{range\;X}=H=\bar{range\;Y}$. (2) There exists an invertible operator A in AlgL such that AX=Y.

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Resveratrol enhances cisplatin-induced apoptosis in human hepatoma cells via glutamine metabolism inhibition

  • Liu, Zhaoyuan;Peng, Qing;Li, Yang;Gao, Yi
    • BMB Reports
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    • 제51권9호
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    • pp.474-479
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    • 2018
  • Cisplatin is one of the most effective chemotherapeutic drugs used in the treatment of HCC, but many patients will ultimately relapse with cisplatin-resistant disease. Used in combination with cisplatin, resveratrol has synergistic effect of increasing chemosensitivity of cisplatin in various cancer cells. However, the mechanisms of resveratrol enhancing cisplatin-induced toxicity have not been well characterized. Our study showed that resveratrol enhances cisplatin toxicity in human hepatoma cells via an apoptosis-dependent mechanism. Further studies reveal that resveratrol decreases the absorption of glutamine and glutathione content by reducing the expression of glutamine transporter ASCT2. Flow cytometric analyses demonstrate that resveratrol and cisplatin combined treatment leads to a significant increase in ROS production compared to resveratrol or cisplatin treated hepatoma cells alone. Phosphorylated H2AX (${\gamma}H2AX$) foci assay demonstrate that both resveratrol and cisplatin treatment result in a significant increase of ${\gamma}H2AX$ foci in hepatoma cells, and the resveratrol and cisplatin combined treatment results in much more ${\gamma}H2AX$ foci formation than either resveratrol or cisplatin treatment alone. Furthermore, our studies show that over-expression of ASCT2 can attenuate cisplatin-induced ROS production, ${\gamma}H2AX$ foci formation and apoptosis in human hepatoma cells. Collectively, our studies suggest resveratrol may sensitize human hepatoma cells to cisplatin chemotherapy via gluta${\gamma}H2AX$mine metabolism inhibition.

SELF-ADJOINT INTERPOLATION ON AX = Y IN $\mathcal{B}(\mathcal{H})$

  • Kwak, Sung-Kon;Kim, Ki-Sook
    • 호남수학학술지
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    • 제30권4호
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    • pp.685-691
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    • 2008
  • Given operators $X_i$ and $Y_i$ (i = 1, 2, ${\cdots}$, n) acting on a Hilbert space $\mathcal{H}$, an interpolating operator is a bounded operator A acting on $\mathcal{H}$ such that $AX_i$ = $Y_i$ for i= 1, 2, ${\cdots}$, n. In this article, if the range of $X_k$ is dense in H for a certain k in {1, 2, ${\cdots}$, n), then the following are equivalent: (1) There exists a self-adjoint operator A in $\mathcal{B}(\mathcal{H})$ stich that $AX_i$ = $Y_i$ for I = 1, 2, ${\cdots}$, n. (2) $sup\{{\frac{{\parallel}{\sum}^n_{i=1}Y_if_i{\parallel}}{{\parallel}{\sum}^n_{i=1}X_if_i{\parallel}}:f_i{\in}H}\}$ < ${\infty}$ and < $X_kf,Y_kg$ >=< $Y_kf,X_kg$> for all f, g in $\mathcal{H}$.

EQUATIONS AX = Y AND Ax = y IN ALGL

  • Jo, Young-Soo;Kang, Joo-Ho;Park, Dong-Wan
    • 대한수학회지
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    • 제43권2호
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    • pp.399-411
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    • 2006
  • Let L be a subspace lattice on a Hilbert space H and X and Y be operators acting on a Hilbert space H. Let P be the projection onto $\frac\;{R(X)}$, where RX is the range of X. If PE = EP for each $E\;\in\;L$, then there exists an operator A in AlgL such that AX = Y if and only if $$sup\{{\parallel}E^{\bot}Yf{\parallel}/{\parallel}E^{\bot}Xf{\parallel}\;:\;f{\in}H,\; E{\in}L}=K\;<\;\infty$$ Moreover, if the necessary condition holds, then we may choose an operator A such that AX = Y and ${\parallel}A{\parallel} = K.$ Let x and y be vectors in H and let $P_x$ be the projection onto the singlely generated space by x. If $P_xE = EP_x$ for each $E\inL$, then the assertion that there exists an operator A in AlgL such that Ax = y is equivalent to the condition $$K_0\;:\;=\;sup\{{\parallel}E^{\bot}y{\parallel}/{\parallel}E^{\bot}x\;:\;E{\in}L}=<\;\infty$$ Moreover, we may choose an operator A such that ${\parallel}A{\parallel} = K_0$ whose norm is $K_0$ under this case.

POSITIVE INTERPOLATION ON Ax = y AND AX = Y IN ALG$\mathcal{L}$

  • Kang, Joo-Ho
    • 호남수학학술지
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    • 제31권2호
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    • pp.259-265
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    • 2009
  • Let $\mathcal{L}$ be a subspace lattice on a Hilbert space $\mathcal{H}$. Let x and y be vectors in $\mathcal{H}$ and let $P_x$ be the projection onto sp(x). If $P_xE$ = $EP_x$ for each E ${\in}\;\mathcal{L}$, then the following are equivalent. (1) There exists an operator A in Alg$\mathcal{L}$ such that Ax = y, Af = 0 for all f in $sp(x)^{\perp}$ and A ${\geq}$ 0. (2) sup ${\frac{{\parallel}E^{\perp}y{\parallel}}{{\parallel}E^{\perp}x{\parallel}}:E{\in}\mathcal{L}}$ < ${\infty}$ < x, y > ${\geq}$ 0. Let X and Y be operators in $\mathcal{B}(\mathcal{H})$. Let P be the projection onto $\overline{rangeX}$. If PE = EP for each E ${\in}\;\mathcal{L}$, then the following are equivalent: (1) sup ${\frac{{\parallel}E^{\perp}Yf{\parallel}}{{\parallel}E^{\perp}Xf{\parallel}}:f{\in}\mathcal{H},E{\in}\mathcal{L}}$ < ${\infty}$ and < Xf, Yf > ${\geq}$ 0 for all f in H. (2) There exists a positive operator A in Alg$\mathcal{L}$ such that AX = Y.