CDC6 association with ORC(1-6) at replication origins

Stable Identifier
Homo sapiens
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CDC6 binds to the origin of replication complex (ORC) by directly interacting with the ORC1 subunit and possibly the ORC2 subunit (Tocilj et al. 2017). CDC6 completes the hexameric ring and the DNA-binding channel of the ORC(1-6) complex, forming an additional ATP hydrolysis site (Tocilj et al. 2017). Formation of the complex between CDC6 and ORC(1-6) is evolutionarily conserved in yeast (Sun et al. 2012; Sun et al. 2013), fruit fly (Bleichert et al. 2015; Bleichert et al. 2018; Schmidt and Bleichert 2020) and human (Tocilj et al. 2017). Interaction of CDC6 with ORC and formation of the pre-replication complex may be facilitated by binding of CDC6 to MCM8 (Volkening and Hoffmann 2005; Wang et al. 2021). MCM8 may simultaneously interact with CDC6 and ORC2 (Volkening and Hoffmann 2005). It is not yet clear if MCM8 primarily functions during replication initiation or replication elongation (Maiorano et al. 2005).

Literature References
PubMed ID Title Journal Year
28112645 Structure of the active form of human origin recognition complex and its ATPase motor module

Li, H, On, KF, Yuan, Z, Elkayam, E, Sun, J, Joshua-Tor, L, Stillman, B, Tocilj, A

Elife 2017
15684404 Involvement of human MCM8 in prereplication complex assembly by recruiting hcdc6 to chromatin

Hoffmann, I, Volkening, M

Mol Cell Biol 2005
25762138 Crystal structure of the eukaryotic origin recognition complex

Botchan, MR, Bleichert, F, Berger, JM

Nature 2015
23851460 Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA

Fernández-Cid, A, Li, H, Samel, SA, Speck, C, Riera, A, Sun, J, Kawakami, H, Evrin, C, Stillman, B

Nat Struct Mol Biol 2013
15707891 MCM8 is an MCM2-7-related protein that functions as a DNA helicase during replication elongation and not initiation

Danis, E, Maiorano, D, Cuvier, O, Mechali, M

Cell 2005
34131285 MCM8 is regulated by EGFR signaling and promotes the growth of glioma stem cells through its interaction with DNA-replication-initiating factors

Song, Y, Han, S, Wang, R, Jiang, Y, Wang, X, Hu, T, Zhang, L, Zhang, D

Oncogene 2021
29899147 Conformational control and DNA-binding mechanism of the metazoan origin recognition complex

Leitner, A, Botchan, MR, Aebersold, R, Bleichert, F, Berger, JM

Proc Natl Acad Sci U S A 2018
32848132 Structural mechanism for replication origin binding and remodeling by a metazoan origin recognition complex and its co-loader Cdc6

Bleichert, F, Schmidt, JM

Nat Commun 2020
22405012 Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy

Li, H, Speck, C, Zech, J, Sun, J, Kawakami, H, Stillman, B

Structure 2012
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