人类抗体重排机制的起源

 重组激活基因（RAG）蛋白介导的抗体重排是脊椎动物适应性免疫系统的核心,抗体重排机制的起源一直是免疫学研究的热点。本研究以有活化石之称的文昌鱼为对象,对多个文昌鱼基因组草图进行深度信息学分析,发现了一个全新DNA转座子ProtoRAG。进一步功能研究表明,ProtoRAG编码的蛋白能够介导自身的转座和宿主DNA的重排,其作用机制与人类抗体蛋白介导的抗体重排机制基本一致。因此,ProtoRAG就是研究人员长期搜寻的祖先RAG转座子的“分子活化石”,该发现为诺贝尔生理学或医学奖获得者利根川进提出的“抗体重排机制转座子起源”假说提供了最有力和最直接的证据。     

ATM stabilizes DNA double-strand-break complexes during V(D)J recombination

The ATM (ataxia-telangiectasia mutated) protein kinase mediates early cellular responses to DNA double-strand breaks (DSBs) generated during metabolic processes or by DNA-damaging agents. ATM deficiency leads to ataxia-telangiectasia, a disease marked by lymphopenia, genomic instability and an increased predisposition to lymphoid malignancies with chromosomal translocations involving lymphocyte antigen receptor loci. ATM activates cell-cycle checkpoints and can induce apoptosis in response to DNA DSBs. However, defects in these pathways of the DNA damage response cannot fully account for the phenotypes of ATM deficiency. Here, we show that ATM also functions directly in the repair of chromosomal DNA DSBs by maintaining DNA ends in repair complexes generated during lymphocyte antigen receptor gene assembly. When coupled with the cell-cycle checkpoint and pro-apoptotic activities of ATM, these findings provide a molecular explanation for the increase in lymphoid tumours with translocations involving antigen receptor loci associated with ataxia-telangiectasia.     

Transposition of hAT elements links transposable elements and V(D)J recombination

Transposons are DNA sequences that encode functions that promote their movement to new locations in the genome. If unregulated, such movement could potentially insert additional DNA into genes, thereby disrupting gene expression and compromising an organism's viability. Transposable elements are classified by their transposition mechanisms and by the transposases that mediate their movement. The mechanism of movement of the eukaryotic hAT superfamily elements was previously unknown, but the divergent sequence of hAT transposases from other elements suggested that these elements might use a distinct mechanism. Here we have analysed transposition of the insect hAT element Hermes in vitro. Like other transposons, Hermes excises from DNA via double-strand breaks between the donor-site DNA and the transposon ends, and the newly exposed transposon ends join to the target DNA. Interestingly, the ends of the donor double-strand breaks form hairpin intermediates, as observed during V(D)J recombination, the process which underlies the combinatorial formation of antigen receptor genes. Significant similarities exist in the catalytic amino acids of Hermes transposase, the V(D)J recombinase RAG, and retroviral integrase superfamily transposases, thereby linking the movement of transposable elements and V(D)J recombination.     

53BP1 facilitates long-range DNA end-joining during V(D)J recombination

Variable, diversity and joining (V(D)J) recombination and class-switch recombination use overlapping but distinct non-homologous end joining pathways to repair DNA double-strand-break intermediates. 53BP1 is a DNA-damage-response protein that is rapidly recruited to sites of chromosomal double-strand breaks, where it seems to function in a subset of ataxia telangiectasia mutated (ATM) kinase-, H2A histone family member X (H2AX, also known as H2AFX)- and mediator of DNA damage checkpoint 1 (MDC1)-dependent events. A 53BP1-dependent end-joining pathway has been described that is dispensable for V(D)J recombination but essential for class-switch recombination. Here we report a previously unrecognized defect in the joining phase of V(D)J recombination in 53BP1-deficient lymphocytes that is distinct from that found in classical non-homologous-end-joining-, H2ax-, Mdc1- and Atm-deficient mice. Absence of 53BP1 leads to impairment of distal V-DJ joining with extensive degradation of unrepaired coding ends and episomal signal joint reintegration at V(D)J junctions. This results in apoptosis, loss of T-cell receptor alpha locus integrity and lymphopenia. Further impairment of the apoptotic checkpoint causes propagation of lymphocytes that have antigen receptor breaks. These data suggest a more general role for 53BP1 in maintaining genomic stability during long-range joining of DNA breaks.     

DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA

Mammals use DNA methylation for the heritable silencing of retrotransposons and imprinted genes and for the inactivation of the X chromosome in females. The establishment of patterns of DNA methylation during gametogenesis depends in part on DNMT3L, an enzymatically inactive regulatory factor that is related in sequence to the DNA methyltransferases DNMT3A and DNMT3B. The main proteins that interact in vivo with the product of an epitope-tagged allele of the endogenous Dnmt3L gene were identified by mass spectrometry as DNMT3A2, DNMT3B and the four core histones. Peptide interaction assays showed that DNMT3L specifically interacts with the extreme amino terminus of histone H3; this interaction was strongly inhibited by methylation at lysine 4 of histone H3 but was insensitive to modifications at other positions. Crystallographic studies of human DNMT3L showed that the protein has a carboxy-terminal methyltransferase-like domain and an N-terminal cysteine-rich domain. Cocrystallization of DNMT3L with the tail of histone H3 revealed that the tail bound to the cysteine-rich domain of DNMT3L, and substitution of key residues in the binding site eliminated the H3 tail-DNMT3L interaction. These data indicate that DNMT3L recognizes histone H3 tails that are unmethylated at lysine 4 and induces de novo DNA methylation by recruitment or activation of DNMT3A2.     

Recombination signal sequences restrict chromosomal V(D)J recombination beyond the 12/23 rule

The genes encoding the variable regions of lymphocyte antigen receptors are assembled from variable (V), diversity (D) and joining (J) gene segments. V(D)J recombination is initiated by the recombinase activating gene (RAG)-1 and -2 proteins, which introduce DNA double-strand breaks between the V, D and J segments and their flanking recombination signal sequences (RSSs). Generally expressed DNA repair proteins then carry out the joining reaction. The conserved heptamer and nonamer sequences of the RSSs are separated by non-conserved spacers of 12 or 23 base pairs (forming 12-RSSs and 23-RSSs). The 12/23 rule, which is mediated at the level of RAG-1/2 recognition and cutting, specifies that V(D)J recombination occurs only between a gene segment flanked by a 12-RSS and one flanked by a 23-RSS. Vbeta segments are appended to DJbeta rearrangements, with little or no direct Vbeta to Jbeta joining, despite 12/23 compatibility of Vbeta 23-RSSs and Jbeta12-RSSs. Here we use embryonic stem cells and mice with a modified T-cell receptor (TCR)beta locus containing only one Dbeta (Dbeta1) gene segment and one Jbeta (Jbeta1) gene cluster to show that the 5' Dbeta1 12-RSS, but not the Jbeta1 12-RSSs, targets rearrangement of a diverse Vbeta repertoire. This targeting is precise and position-independent. This additional restriction on V(D)J recombination has important implications for the regulation of variable region gene assembly and repertoire development.     

铈钒杂多化合物(NH4)Ce2V3O11(NO3)2·5H2O的合成与表征

首次合成了稀土元素铈 ( )与钒的二元杂多化合物 ,确定其组成为 (NH4 ) Ce2 V3O11(NO3) 2 · 5 H2 O,并用元素分析、红外、紫外、热分析、X-射线粉末衍射等方法对其进行了表征 .此外对它的催化行为也进行了初步研究.     

稀土配合物[Er(Ala)2(Im)(H2O)](ClO4)3的合成、表征与热分析

合成了稀土高氯酸盐与咪唑(Im)、L-α-丙氨酸(A la)的配合物晶体.经傅立叶变换红外光谱(FT-IR)、元素分析和化学分析测定后确定其组成为[Er(A la)2(Im)(H2O)](C lO4)3.用差示扫描量热法(DSC)在高纯流动N2气氛下测定了配合物的热分解数据,配合物的热分解过程由两个放热峰组成,配合物开始分解的温度为494.7 K,峰顶温度为547.3K和628.4K,热分解焓为2 544 kJ/mol和1 006 kJ/mol,测定结果表明配合物有较高的热稳定性.     

铜配合物[Cu(C3N2H3)2(H2NC6H4SO3)2(H2O)2]·2H2O的合成和晶体结构

合成了一种新的铜配合物[Cu(C3N2H3)2(H2NC6H4SO3)2(H2O)2]·2H2O,经元素分析和X-射线衍射得该化合物的分子式为C18H26CuN6O10S2,该晶体属单斜晶系,空间群为P 121／n,晶胞参数为a=7．2928(15) A,b=15．635(3)A,c=11．361(2)A;α=γ=90°,β=104．94(3)°;Z=2;DC=1．629 mg／m3;F(000)= 634;对于可观测衍射点的R1=0．0548,wR2=0．1516,S=1．014;最终差图中最大电子密度峰值和洞值分别为0．968e．A-3和-0．465e．A-3．两个对氨基苯磺酸和两个吡唑各自提供一个N原子、另有两个H2O分别与 Cu2 配位,Cu2 的配位多面体为畸变八面体．     

稀土配合物[Nd(C3H7NO2)2(C3H4N2)(H2O)](ClO4)3的合成与热分析

合成了高氯酸钕与咪唑、DL-α-丙氨酸的配合物晶体.用傅立叶变换红外光谱(FT-IR)、元素分析和化学分析确定其组成为[Nd(C3H7NO2)2(C3H4N2)(H2O)](Cl4)3.用差示扫描量热法(DSC)对配合物的热稳定性进行了研究,发现配合物有较高的热稳定性.     

稀土配合物[Nd(C3H7NO2)2(C3H4N2)(H2O)](ClO4)3的合成、表征与热分析

合成了高氯酸钕与咪唑、DL-α-丙氨酸的配合物晶体。经傅立叶变换红外光谱(FT-IR)分别测定配体和配合物的红外光谱．以及配合物的元素分析和化学分析．测定后确定其组成为[Nd(C3H7NO2)2(C3H4N2)-(H2O)](ClO4)3。用差示扫描量热法(DSC)对配合物的热稳定性进行了研究，发现配合物的热分解是由两个相连的阶段组成并有部分重叠。     

sl(2,C)到其单模V(3)和V(4)的局部导子

将李代数到伴随模局部导子的概念推广到任意有限维模, 从而将一般线性李代数sl(2,C)到其任意单模的局部导子求解问题等价地转化为解相关线性方程组, 进而利用系数矩阵的秩与增广矩阵的秩相等, 确定了3维单李代数sl(2,C)到两类单模V(3)和V(4)的局部导子空间.     

稀土配合物[La(C3H7NO2)3(C3H4N2)(H2O)](ClO4)3的合成、表征与热分析

合成了高氯酸镧与咪唑、DL-α-丙氨酸的配合物晶体．经傅立叶变换红外光谱、元素分析扣化学分析测定后确定其组成为[La(C3H7NO2)3(C3H4N2)(H2O)](ClO4)3用差示扫描量热法对配合物的热稳定性进行了研究，发现配合物有较高的热稳定性．