Reactome | Formation of ORC(1-5) complex

Formation of ORC(1-5) complex

Stable Identifier

R-HSA-68611

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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ORC1 binds to the ORC(2-5) complex in the nucleus to form a stable ORC(1-5) complex (Radichev et al. 2006; Ghosh et al. 2011). ORC1 is necessary for the association of the ORC(2-5) complex to chromatin (Radichev et al. 2006). 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. Binding of ORC1 remodels the WHD of ORC2, moving it away from the central channel and partially relieving the autoinhibition (Cheng et al. 2020, Jaremko et al. 2020). Several dynamic structures of the ORC(1-5) complex have been revealed by cryo-electron microscopy (cryoEM), which depend on the presence of DNA and ATP (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
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
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