Formation of ORC(2-5) complex

Stable Identifier
R-HSA-68610
Type
Reaction
Species
Homo sapiens
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ORC4 forms a complex with the heterotrimer of ORC2, ORC3 and ORC5. The presence of ATP is required for the formation of this complex (Ranjan and Gossen 2006; Siddiqui and Stillman 2007).

While ORC2 (Radichev et al. 2006) and ORC3 (Brand et al. 2007) both possess a nuclear localization signal (NLS), no nuclear localization signal has been reported in ORC4 nor ORC5. ORC2 and ORC3 are known to associate both in the cytosol and in the nucleus (Brand et al. 2007). It is plausible that the ORC(2-5) complex forms in the cytosol and then translocates to the nucleus (Ohta et al. 2003, Ghosh et al. 2011), but additional experimental evidence is needed.

The ORC(2-5) complex exhibits a tightly autoinhibited conformation, with the winged-helix domain (WHD) of ORC2 completely blocking the central DNA-binding channel (Cheng et al. 2020, Jaremko et al. 2020).

Literature References
PubMed ID Title Journal Year
16762929 Genetic analysis of human Orc2 reveals specific domains that are required in vivo for assembly and nuclear localization of the origin recognition complex

Radichev, I, Zhao, Y, Vassilev, A, Kwon, SW, DePamphilis, ML

J Biol Chem 2006
16549788 A structural role for ATP in the formation and stability of the human origin recognition complex

Gossen, M, Ranjan, A

Proc Natl Acad Sci U S A 2006
32808929 The dynamic nature of the human origin recognition complex revealed through five cryoEM structures

On, KF, Joshua-Tor, L, Thomas, DR, Stillman, B, Jaremko, MJ

Elife 2020
21555516 Assembly of the human origin recognition complex occurs through independent nuclear localization of its components

Ghosh, S, Zhao, Y, Vassilev, AP, Zhang, J, DePamphilis, ML

J Biol Chem 2011
17716973 ATP-dependent assembly of the human origin recognition complex

Siddiqui, K, Stillman, B

J Biol Chem 2007
33298899 Structural insight into the assembly and conformational activation of human origin recognition complex

Wang, X, Cheng, J, Gao, N, Zhai, Y, Hu, J, Li, N

Cell Discov 2020
17680271 Interactions and subcellular distribution of DNA replication initiation proteins in eukaryotic cells

Faul, T, Brand, N, Grummt, F

Mol Genet Genomics 2007
12909626 The ORC1 cycle in human cells: II. Dynamic changes in the human ORC complex during the cell cycle

Tatsumi, Y, Fujita, M, Ohta, S, Obuse, C, Tsurimoto, T

J Biol Chem 2003
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