Cdc7 Antibody

• 产品编号：CST-3603S      品牌：CST       原厂货号：3603S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

 Cdc7 Antibody能够检测内源性cdc7总蛋白。该多克隆抗体是由合成的人源的针对cdc7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)。转运蛋白-β(5)调节cdc7蛋白的核转运，它与起始复合物的结合依赖于其定位的调节，三个结构域核定位序列(NLS)、核滞留序列(NRS)和核输出序列(NES)影响其定位。研究显示人类肿瘤细胞系和组织中cdc7 和dbf4的表达水平升高；cdc7的化学抑制剂可以阻碍肿瘤细胞中DNA复制和细胞凋亡(8)。Cdc7也参与激活ATR/Chk1以响应DNA损伤(9,10)。

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. Kim, B.J. and Lee, H. (2006) J Biol Chem 281, 12041-9.
6. Kim, B.J. et al. (2007) J Biol Chem 282, 30029-38.
7. Bonte, D. et al. (2008) Neoplasia 10, 920-31.
8. Montagnoli, A. et al. (2008) Nat Chem Biol 4, 357-65.
9. Heffernan, T.P. et al. (2007) J Biol Chem 282, 9458-68.
10. Kim, J.M. et al. (2008) Oncogene 27, 3475-82.

原厂资料：

Specificity / Sensitivity

Cdc7 Antibody detects endogenous levels of total cdc7 protein.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues near the amino terminus of human cdc7.

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). 
 The import of cdc7 to the nucleus is regulated by importin-β (5) and its binding to the origin of replication is dependent on the regulation of its localization via three domains, a nuclear localization sequence (NLS), a nuclear retention sequence (NRS) and a nuclear export sequence (NES) (6). 
 Expression of cdc7 and dbf4 has been shown to be increased in human cancer cell lines and tissue (7); a chemical inhibitor of cdc7 blocks initiation of DNA replication and causes apoptosis in cancer cells (8). 
 Cdc7 is also involved in activating ATR/Chk1 in response to DNA damage (9,10).

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. Kim, B.J. and Lee, H. (2006) J Biol Chem 281, 12041-9.
6. Kim, B.J. et al. (2007) J Biol Chem 282, 30029-38.
7. Bonte, D. et al. (2008) Neoplasia 10, 920-31.
8. Montagnoli, A. et al. (2008) Nat Chem Biol 4, 357-65.
9. Heffernan, T.P. et al. (2007) J Biol Chem 282, 9458-68.
10. Kim, J.M. et al. (2008) Oncogene 27, 3475-82.

注意事项：

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