Cdc6 (C42F7) Rabbit mAb

• 产品编号：CST-3387S      品牌：CST       原厂货号：3387S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

Cdc6 (C42F7) Rabbit mAb能够检测内源性cdc6总蛋白。该单克隆抗体是由合成的人源的针对cdc6蛋白氨基末端肽段免疫动物生产的。哺乳动物细胞的DNA复制启动是一个高度协调的过程，从而保证了每次细胞分裂中基因组只复制一次。复制的起源分散在整个基因组中，其活性主要通过前复制因子和复制因子的连续结合来调控。起始识别复合体(ORC)被认为可以结合整个细胞周期的染色质(1,2)。前复制复合体(Pre-RC)在有丝分裂末期/G1早期随着CDT1和cdc6的结合而形成，允许异源六聚化的MCM2-7复合体的结合。MCM复合体被认为是一种复制解旋酶，而pre-RC的形成参与染色质许可。随后的DNA复制起始需要S期促进激酶cdk2 和cdc7的激活。Cdc7(只有在复合体中伴随其调节亚基dbf4时才是活跃的)能够磷酸化结合染色质的MCM蛋白并允许复制因子cdc45和DNA聚合酶的结合(3,4)。复制许可部分由静止期细胞中cdc6的降解来控制。通过cdk2磷酸化的cdc6阻止其降解，允许前复制复合体的形成(5)。新近发现cdc6在S期内p21 Waf1/Cip依赖的DNA损伤过程中发挥重要作用(6,7)。Cdc6 和CDT1可以被泛素蛋白酶体通路降解以响应再复制相关的DNA损伤(8)。

1. Okuno, Y. et al. (2001) EMBO J 20, 4263-77.
2. McNairn, A.J. et al. (2005) Exp Cell Res 308, 345-56.
3. Bell, S.P. and Dutta, A. (2002) Annu Rev Biochem 71, 333-74.
4. Tsuji, T. et al. (2006) Mol Biol Cell 17, 4459-72.
5. Mailand, N. and Diffley, J.F. (2005) Cell 122, 915-26.
6. Kan, Q. et al. (2008) J Biol Chem 283, 17864-72.
7. Kan, Q. et al. (2008) Proc Natl Acad Sci USA 105, 4757-62.
8. Hall, J.R. et al. (2008) J Biol Chem 283, 25356-63.

原厂资料：

Specificity / Sensitivity

Cdc6 (C42F7) Rabbit mAb detects endogenous levels of total cdc6 protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues near the amino terminus of human cdc6.

Background

The initiation of DNA replication in mammalian cells is a highly coordinated process that ensures duplication of the genome only once per cell division cycle. Origins of replication are dispersed throughout the genome, and their activities are regulated via the sequential binding of pre-replication and replication factors. The origin recognition complex (ORC) is thought to be bound to chromatin throughout the cell cycle (1,2). The pre-replication complex (Pre-RC) forms in late mitosis/early G1 phase beginning with the binding of CDT1 and cdc6 to the origin, which allows binding of the heterohexameric MCM2-7 complex. The MCM complex is thought to be the replicative helicase, and formation of the pre-RC is referred to as chromatin licensing. Subsequent initiation of DNA replication requires the activation of the S-phase promoting kinases cdk2 and cdc7. Cdc7, which is active only in complex with its regulatory subunit dbf4, phosphorylates MCM proteins bound to chromatin and allows binding of the replication factor cdc45 and DNA polymerase (3,4). 
 Replication licensing is controlled in part by the degradation of cdc6 in quiescent cells. Phosphorylation of cdc6 by cdk2 prevents its degradation, allowing pre-replication complexes to form (5). Cdc6 has recently been shown to play an important role in the intra-S-phase p21 Waf1/Cip1-dependent DNA damage response (6,7). Both cdc6 and CDT1 are degraded by the ubiquitin proteasome pathway in response to DNA damage associated with re-replication (8).

1. Okuno, Y. et al. (2001) EMBO J 20, 4263-77.
2. McNairn, A.J. et al. (2005) Exp Cell Res 308, 345-56.
3. Bell, S.P. and Dutta, A. (2002) Annu Rev Biochem 71, 333-74.
4. Tsuji, T. et al. (2006) Mol Biol Cell 17, 4459-72.
5. Mailand, N. and Diffley, J.F. (2005) Cell 122, 915-26.
6. Kan, Q. et al. (2008) J Biol Chem 283, 17864-72.
7. Kan, Q. et al. (2008) Proc Natl Acad Sci USA 105, 4757-62.
8. Hall, J.R. et al. (2008) J Biol Chem 283, 25356-63.

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 antibody.