• 제목/요약/키워드: V(D)J recombination

검색결과 14건 처리시간 0.021초

DNA-dependent Protein Kinase Mediates V(D)J Recombination via RAG2 Phosphorylation

  • Hah, Young-Sool;Lee, Jung-Hwa;Kim, Deok-Ryong
    • BMB Reports
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    • 제40권3호
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    • pp.432-438
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    • 2007
  • V(D)J recombination, a site-specific gene rearrangement process occurring during the lymphocyte development, begins with DNA double strand breaks by two recombination activating gene products (RAG1/2) and finishes with the repair process by several proteins including DNA-dependent protein kinase (DNA-PK). In this report, we found that RAG2 was specifically phosphorylated by DNA-PK at the $365^{th}$ serine residue, and this phosphorylated RAG2 affected the V(D)J recombination activity in cells in the GFP expression-based assay. While the V(D)J recombination activity between wild-type RAG2 and mutant S365A RAG2 in the assay using a signal joint substrate was undistinguishable in DNA-PK deficient cells (M059J), the activity with wild-type RAG2 was largely increased in DNA-PK proficient cells (M059K) in comparison with mutant RAG2, suggesting that RAG2 phosphorylation by DNA-PK plays a crucial role in the signal joint formation during V(D)J recombination.

Recombination Activating Gene 1 Product Alone Possesses Endonucleolytic Activity

  • Kim, Deok-Ryong
    • BMB Reports
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    • 제36권2호
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    • pp.201-206
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    • 2003
  • Two lymphoid-specific proteins, RAG1 and RAG2, are required for the initiation of the V(D)J recombination in vitro. The V(D)J cleavage that is mediated by RAG proteins at the border between the coding and signal sequences results in the production of a hairpin at the coding end and a double-stranded break at the signal end. Two hairpin coding ends are re-opened, modified, and sealed; whereas, the signal ends are directly ligated. Here I report that only RAG1 can carry out a distinct endonucleolytic activity in vitro using an oligonucleotide substrate that is tethered by a short single-stranded DNA. The purified RAG1 protein alone formed a nick at the near position to the recombination signal sequence. This endonucleolytic activity was eliminated by immunoprecipitation using the RAG1-specific antibody, and required the 3'-hydroxy group. All of the RAG1 mutants that were incapable of the nick and hairpin formation in the V(D)J cleavage analysis also showed this new endonucleolytic activity. This suggests that the nicking activity that was observed might be functionally different from the nick formation in the V(D)J cleavage.

The Yin and Yang of RNA surveillance in B lymphocytes and antibody-secreting plasma cells

  • Lambert, Jean-Marie;Srour, Nivine;Delpy, Laurent
    • BMB Reports
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    • 제52권12호
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    • pp.671-678
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    • 2019
  • The random V(D)J recombination process ensures the diversity of the primary immunoglobulin (Ig) repertoire. In two thirds of cases, imprecise recombination between variable (V), diversity (D), and joining (J) segments induces a frameshift in the open reading frame that leads to the appearance of premature termination codons (PTCs). Thus, many B lineage cells harbour biallelic V(D)J-rearrangements of Ig heavy or light chain genes, with a productively-recombined allele encoding the functional Ig chain and a nonproductive allele potentially encoding truncated Ig polypeptides. Since the pattern of Ig gene expression is mostly biallelic, transcription initiated from nonproductive Ig alleles generates considerable amounts of primary transcripts with out-of-frame V(D)J junctions. How RNA surveillance pathways cooperate to control the noise from nonproductive Ig genes will be discussed in this review, focusing on the benefits of nonsense- mediated mRNA decay (NMD) activation during B-cell development and detrimental effects of nonsense-associated altered splicing (NAS) in terminally differentiated plasma cells.

바다송사리(Oryzias dancena)의 재조합활성화 유전자 RAG1/2의 분자 특성 및 개체발생학적 발현 패턴 (Molecular Characterization and Ontogenetic Expression Patterns of Recombination Activating Genes (RAG1/2) in Marine Medaka Oryzias dancena)

  • 김태수;박주환;남윤권;김찬희
    • 한국수산과학회지
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    • 제57권3호
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    • pp.239-252
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    • 2024
  • Recombination activating genes (RAGs) play a crucial role in initiating V(D)J recombination, which is essential for developing adaptive immunity in vertebrates. In this study, we cloned and characterized RAG1/2 cDNA from the marine medaka Oryzias dancena (OdRAG1/2) and investigated their mRNA expression patterns during ontogenetic developmental stages. The OdRAG1 and OdRAG2 cDNA contained open reading frames (ORFs) encoding proteins containing 1,078 and 531 amino acids, respectively. Multiple sequence alignment and phylogenetic analysis revealed that OdRAG1 and OdRAG2 are highly conserved with their corresponding orthologs, featuring distinct core and non-core regions. Notably, expression analysis showed that, in contrast to other fish RAGs studied, OdRAG1/2 expression peaked at 0 days post-hatching (DPH). Additionally, for the expression of T and B cell differentiation markers, CD3γ and CD20, also peaked at 0 DPH. Collectively, adaptive immunity in O. dancena potentially begins during embryonic development, which is critical for V(D)J recombination and essential immune component development, suggesting the early ontogenetic stage interactions between innate and adaptive immunity.

LaAlO3에 대한 열자극발광 스펙트럼의 광학적 분석 (A Measurement and Analysis of Thermoluminescence Spectra of LaAlO3)

  • 이정일;문정학;김덕훈
    • 한국안광학회지
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    • 제4권2호
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    • pp.141-146
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    • 1999
  • 단결정 $LaAlO_3$의 열자극발광을 온도, 파장, 발광강도의 3차원 데이터로 측정하였고, 이를 분석하였다. $LaAlO_3$는 YBCO(초전도체) 또는 각종 반도체의 성장기판으로 많이 활용되고 있다. 온도, 파장, 발광강도의 3차원 데이터를 얻으므로써 활성화 에너지 뿐만 아니라, 기존의 온도대 발광곡선(glow curve) 분석에서 그 정보를 알기 힘들었던, 재결합준위(recombination center)의 에너지를 결정할 수 있었다. 이는 특정 피크온도에서의 파장대 발광강도 데이터를 Franck-Condon 모델을 이용하여 곡선 춤법으로 분석하여 얻을 수 있다. 온도대 발광강도곡선(glow curve)을 수치해석에 의한 곡선맞춤법으로 분석한 결과 세 개의 발광곡선이 중첩되어 있음을 알게되었으며, 각각에 대한 활성화 에너지는 0.54eV, 0.91eV, 1.02eV 였다. 재결합준위의 에너지는 2.04eV, 2.75eV 였다.

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Ga/(In+Ga) 함량비에 따른 $Cu(In,Ga)Se_2$ 박막의 국소적 영역에서의 표면 퍼텐셜과 전류-전압 특성 연구 (Local surface potential and current-voltage behaviors of $Cu(In,Ga)Se_2$ thin-films with different Ga/(In+Ga) content)

  • 김지영;정아름;조윌렴;조현준;김대환;성시준;황대규;강진규;이동하
    • 한국태양에너지학회:학술대회논문집
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    • 한국태양에너지학회 2012년도 춘계학술발표대회 논문집
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    • pp.149-152
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    • 2012
  • $Cu(In,Ga)Se_2$ (CIGS) is one of the most promising photovoltaic materials because of large conversion efficiency which has been achieved with an optimum Ga/(In+Ga) composition in $CuIn_{1-x}Ga_xSe_2$ (X~0.3). The Ga/(In+Ga) content is important to determine band gap, solar cell performances and carrier behaviors at grain boundary (GB). Effects of Ga/(In+Ga) content on physical properties of the CIGS layers have been extensively studied. In previous research, it is reported that GB is not recombination center of CIGS thin-film solar cells. However, GB recombination and electron-hole pair behavior studies are still lacking, especially influence of with different X on CIGS thin-films. We obtained the GB surface potential, local current and I-V characteristic of different X (00.7 while X~0.3 showed higher potential than 100 mV on GBs. Higher potential on GBs appears positive band bending. It can decrease recombination loss because of carrier separation. Therefore, we suggest recombination and electron-hole behaviors at GBs depending on composition of X.

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DNA-Dependent Protein Kinase Catalytic Subunit (DNA-PKcs): Beyond the DNA Double-Strand Break Repair

  • Ye-Rim Lee;Gi-Sue Kang;Taerim Oh;Hye-Ju Jo;Hye-Joon Park;G-One Ahn
    • Molecules and Cells
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    • 제46권4호
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    • pp.200-205
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    • 2023
  • DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a member of the phosphatidylinositol 3-kinase-related kinase family is a well-known player in repairing DNA double-strand break through non-homologous end joining pathway. This mechanism has allowed us to understand its critical role in T and B cell development through V(D)J recombination and class switch recombination, respectively. We have also learned that the defects in these mechanisms lead to the severely combined immunodeficiency (SCID). Here we highlight some of the latest evidence where DNA-PKcs has been shown to localize not only in the nucleus but also in the cytoplasm, phosphorylating various proteins involved in cellular metabolism and cytokine production. While it is an exciting time to unveil novel functions of DNA-PKcs, one should carefully choose experimental models to study DNA-PKcs as the experimental evidence has been shown to differ between cells of defective DNA-PKcs and those of DNA-PKcs knockout. Moreover, while there are several DNA-PK inhibitors currently being evaluated in the clinical trials in an attempt to increase the efficacy of radiotherapy or chemotherapy, multiple functions and subcellular localization of DNA-PKcs in various types of cells may further complicate the effects at the cellular and organismal level.

High energy swift heavy ion irradiation and annealing effects on DC electrical characteristics of 200 GHz SiGe HBTs

  • Hegde, Vinayakprasanna N.;Praveen, K.C.;Pradeep, T.M.;Pushpa, N.;Cressler, John D.;Tripathi, Ambuj;Asokan, K.;Prakash, A.P. Gnana
    • Nuclear Engineering and Technology
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    • 제51권5호
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    • pp.1428-1435
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    • 2019
  • The total ionizing dose (TID) and non ionizing energy loss (NIEL) effects of 100 MeV phosphorous ($P^{7+}$) and 80 MeV nitrogen ($N^{6+}$) ions on 200 GHz silicon-germanium heterojunction bipolar transistors (SiGe HBTs) were examined in the total dose range from 1 to 100 Mrad(Si). The in-situ I-V characteristics like Gummel characteristics, excess base current (${\Delta}I_B$), net oxide trapped charge ($N_{OX}$), current gain ($h_{FE}$), avalanche multiplication (M-1), neutral base recombination (NBR) and output characteristics ($I_C-V_{CE}$) were analysed before and after irradiation. The significant degradation in device parameters was observed after $100MeV\;P^{7+}$ and $80MeV\;N^{6+}$ ion irradiation. The $100MeV\;P^{7+}$ ions create more damage in the SiGe HBT structure and in turn degrade the electrical characteristics of SiGe HBTs more when compared to $80MeV\;N^{6+}$. The SiGe HBTs irradiated up to 100 Mrad of total dose were annealed from $50^{\circ}C$ to $400^{\circ}C$ in different steps for 30 min duration in order to study the recovery of electrical characteristics. The recovery factors (RFs) are employed to analyse the contribution of room temperature and isochronal annealing in total recovery.

Primary damage of 10 keV Ga PKA in bulk GaN material under different temperatures

  • He, Huan;He, Chaohui;Zhang, Jiahui;Liao, Wenlong;Zang, Hang;Li, Yonghong;Liu, Wenbo
    • Nuclear Engineering and Technology
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    • 제52권7호
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    • pp.1537-1544
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    • 2020
  • Molecular dynamics (MD) simulations were conducted to investigate the temperature effects on the primary damage in gallium nitride (GaN) material. Five temperatures ranging from 300 K to 900 K were studied for 10 keV Ga primary knock-on atom (PKA) with inject direction of [0001]. The results of MD simulations showed that threshold displacement energy (Ed) was affected by temperatures and at higher temperature, it was larger. The evolutions of defects under various temperatures were similar. However, the higher temperature was found to increase the peak number, peak time, final time and recombination efficiency while decreasing the final number. With regard to clusters, isolated point defects and little clusters were common clusters and the fraction of point defects increased with temperature for vacancy clusters, whereas it did not appear in the interstitial clusters. Finally, at each temperature, the number of Ga interstitial atoms was larger than that of N and besides that, there were other different results of specific types of split interstitial atoms.

LiF:Mg, Cu, Na, Si TL 물질의 열자극발광스펙트럼 측정 및 분석 (The Measurement and Analysis of LiF:Mg, Cu, Na, Si TL Material by Thermoluminescence Spectrum)

  • 이정일;문정학;김덕훈
    • 한국안광학회지
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    • 제6권1호
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    • pp.149-153
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    • 2001
  • LiF:Mg, Cu, Na, Si TL 물질의 열자극발광을 온도대 파장대 발광강도의 3차원으로 측정하여 분석하였다. 온도대 발광강도곡선(glow curve)은 각 온도에서 파장별 발광강도데이터를 적분하여 구성하였고, 이를 분석하여 트랩에 관계되는 여러가지 파라미터들을 결정하였다. 발광곡선의 분석은 일반차 모델의 TL 강도 표현식을 기본함수로 하여 컴퓨터화된 발광곡선 분해(Computerized Glow Curve Deconvolution: CGCD)기법을 이용하였고, 그 결과 LiF:Mg, Cu, Na, Si TL 물질의 열자극발광곡선은 정점온도 333 K, 374 K 426 K, 466 K, 483 K 그리고 516 K를 갖는 6개의 개별적인 발광곡선들로 구성되어 있음을 확인하였다. 주 피크(main peak)인 456 K 발광곡선에 대하여 활성화에너지는 2.06 eV, 발광차수는 1.05로 밝혀졌다. 발광스펙트럼 분석결과 LiF:Mg, Cu, Na, Si TL 물질은 3개의 재결합준위 1.80 eV, 2.88 eV 그리고 3.27 eV를 가지는 것으로 판명되었다. 이 중 약 2.88 eV 준위가 지배적이고 다음으로 3.27eV 준위에서 발광이 일어나며 1.80 eV 준위는 극히 미약하나 분명한 존재를 확인하였다.

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