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).
Radichev, I, Zhao, Y, Vassilev, A, Kwon, SW, DePamphilis, ML
Gossen, M, Ranjan, A
On, KF, Joshua-Tor, L, Thomas, DR, Stillman, B, Jaremko, MJ
Ghosh, S, Zhao, Y, Vassilev, AP, Zhang, J, DePamphilis, ML
Siddiqui, K, Stillman, B
Wang, X, Cheng, J, Gao, N, Zhai, Y, Hu, J, Li, N
Faul, T, Brand, N, Grummt, F
Tatsumi, Y, Fujita, M, Ohta, S, Obuse, C, Tsurimoto, T
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