MRN Complex Antibody Sampler Kit

• 产品编号：CST-8344S      品牌：Cell Signaling Technology       原厂货号：8344S
• 产品分类：抗体 > 一抗 > 复合抗体试剂盒
• 应用分类：

其它组分：

描述：

所有抗体均能检测其内源性靶蛋白。总多克隆抗体是由合成的人源的针对Rad50蛋白氨基末端肽段或p95/NBS1蛋白羧基末端肽段免疫兔生产的。激活状态特异性多克隆抗体是由合成的人源的针对p95/NBS1蛋白丝氨酸（343位）的磷酸化肽段或 Mre11蛋白丝氨酸（676位）的磷酸化肽段免疫兔生产的。多克隆抗体采用蛋白A和多肽亲和层析技术纯化生产。多克隆抗体是由合成的人源的针对Mre11A蛋白的赖氨酸（496位）的肽段免疫动物生产的。MRN Complex Antibody Sampler Kit能够经济地检测每个靶蛋白。该试剂盒内含足够4次western blot实验的一抗和二抗。 Mre11-Rad50-Nbs1 (MRN)复合物是一个重要的基因组维护介质，在减数分裂时、染色体末端的端粒稳定和细胞应答DNA损伤过程中起着重要作用(1-5)。Mre11和Rad50亚基的同源二聚体形成的四聚体核心，直接结合DNA并与NBS1蛋白亚基联合(6)。该复合体作为DNA损伤传感器并定位于DNA双链断裂处。在这些DNA损伤中，MRN复合物拴住DNA末端，并通过Mre11的核酸内切酶和外切酶的活性处理自由链。除了刺激同源重组和非同源末端连接修复DNA途径以外，MRN激活DNA损伤检验点信号级联反应调节细胞周期进程。在某些情况下，MRN为ATM激活和下游p53、BRCA1和Chk2的磷酸化所必需(7)。ATM还可以磷酸化Mre11，Rad50和NBS1(也称为P95和Nibrin)。值得注意的是，NBS1 Ser343和MRE11 Ser676被ATM磷酸化。磷酸化调节蛋白功能和与许多介质的相关性，其中包括53BP1，RPA，hSSB1，TRF2，BRCA1，FANCD2，CTP1，组蛋白H2AX，MDC1和WRN解旋酶。每个亚基对哺乳动物的胚胎发育是必不可少的，作为纯合子无效突变中的Mre11，NBS1，或Rad50蛋白对小鼠是致命的。此外，MRN复合物的功能为淋巴细胞发育中RAG-1和RAG-2的重组酶启动的抗原受体基因重组所必需。在人类中，Mre11和NBS1基因突变导致染色体不稳定和辐射敏感性并分别与共济失调毛细血管扩张症状症(ATLD)和Nijmegen断裂综合征(NBS)相关(8)。已经证实具有MRN复合物基因内突变的细胞会发生基因组不稳定和癌症。

原厂资料：

Specificity / Sensitivity

Antibodies detect endogenous levels of their respective proteins.

Source / Purification

Total polyclonal antibodies are produced by immunizing rabbits with synthetic peptides corresponding to the amino terminus of human Rad50 or carboxy-terminal residues of human p95/NBS1. Activation state-specific polyclonal antibodies are produced by immunizing rabbits with synthetic phosphopeptides corresponding to residues surrounding Ser343 of human p95/NBS1 or Ser676 of human Mre11. Polyclonal antibodies are purified by protein A and peptide affinity chromatography. Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Lys496 of human Mre11A.

Description

MRN Complex Antibody Sampler Kit offers an economical way of detecting each target protein. The kit contains enough primary and secondary antibody to perform four western blot experiments with each primary antibody.

Background

The Mre11-Rad50-Nbs1 (MRN) complex is a key mediator of genome maintenance, playing important roles in meiosis, telomere stability at the ends of chromosomes, and the cellular responses to DNA damage (1-5). Homodimers of the Mre11 and Rad50 subunits form a tetramer core that binds directly to DNA and associates with the Nbs1 subunit (6). The complex functions as a sensor of DNA damage and localizes to DNA double-strand breaks. At these DNA lesions, the MRN complex tethers DNA ends and processes free strands via the endonuclease and exonuclease activities of Mre11. In addition to stimulating both homologous recombination and nonhomologous end joining repair DNA pathways, MRN activates DNA damage checkpoint signaling cascades regulating cell cycle progression. In some contexts, MRN is required for ATM activation and downstream phosphorylation of p53, BRCA1, and Chk2 (7). ATM also phosphorylates Mre11, Rad50, and Nbs1 (also known as p95 and Nibrin). Notably, Nbs1 Ser343 and Mre11 Ser676 are phosphorylated by ATM. Phosphorylation modulates function and association with many mediators, some of which include 53BP1, RPA, hSSB1, TRF2, BRCA1, FANCD2, CtP1, Histone H2AX, MDC1, and WRN helicase. Each subunit is essential for mammalian embryonic development, as mice with homozygous-null mutations in Mre11, Nbs1, or Rad50 are lethal. Furthermore, MRN complex function is required in developing lymphocytes for antigen receptor gene recombination initiated by the Rag-1 and Rag-2 recombinases. In humans, Mre11 and Nbs1 mutations cause chromosomal instability and radiosensitivity and are associated with ataxia-telangiectasia-like disorder (ATLD) and Nijmegen breakage syndrome (NBS), respectively (8). Genomic instability and cancer have been shown to develop in cells with genetic mutations within MRN complex genes.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150
mM NaCl, 100 µg/ml BSA, 50% glycerol and less than 0.02%
sodium azide. Store at –20°C. Do not aliquot the antibodies.