Reactome | Formation of ORC(2-5) complex

Formation of ORC(2-5) complex

Stable Identifier

R-HSA-68610

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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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