Assembly of the ORC complex at the origin of replication

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Homo sapiens
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In Saccharomyces cerevisiae, the entire ORC complex is constitutively bound to the origin of replication. However, in mammalian cells, Orc1, and possibly other Orc subunits, dissociate from origins of replication, while Orc2 remains stably associated with chromatin across the cell cycle. The first step in formation of the pre-RC is assembly of the hexameric Origin Recognition Complex (ORC) at the origin of replication. Recent work on human (Hs) ORC has suggested that the heterohexamer assembles in an ordered manner. HsOrc2 appears to be constitutively bound to origins of replication. HsOrc2 and HsOrc3 form a complex that interacts with HsOrc4 and HsOrc5. Recruitment of HsOrc5 into the complex is important for the association of HsOrc1. HsOrc6 is also capable of interacting with the core HsOrc2:3:4:5 complex, but not smaller complexes. Interestingly, HsOrc1 and a subunit of the Mcm2-7 complex (HsMcm2) interact with a histone acetyltransferase, HsHBO1 (Bell & Stillman 1992; Diffley et al. 1994; Lee & Bell 1997; Wenger et al. 1975; Li & DePamphili;s 2001; Dhar et al. 2001; Vashee et al, 2001; Iizuka & Stillman 1999 Burke et al. 2001).

Literature References
PubMed ID Title Journal Year
8044842 Two steps in the assembly of complexes at yeast replication origins in vivo.

Diffley, JF, Cocker, JH, Dowell, SJ, Rowley, A

Cell 1994
11323433 Assembly of the human origin recognition complex.

Vashee, S, Simancek, P, Challberg, MD, Kelly, TJ

J Biol Chem 2001
1579162 ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex.

Bell, SP, Stillman, B

Nature 1992
11278932 Replication factors MCM2 and ORC1 interact with the histone acetyltransferase HBO1.

Burke, TW, Cook, JG, Asano, M, Nevins, JR

J Biol Chem 2001
10438470 Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein.

Iizuka, M, Stillman, B

J Biol Chem 1999
11395502 Architecture of the human origin recognition complex.

Dhar, SK, Delmolino, L, Dutta, A

J Biol Chem 2001
1110244 Forearm blood flow during body temperature transients produced by leg exercise.

Wenger, CB, Roberts, MF, Stolwijk, JA, Nadel, ER

J Appl Physiol 1975
11739726 Mammalian Orc1 protein is selectively released from chromatin and ubiquitinated during the S-to-M transition in the cell division cycle.

Li, CJ, DePamphilis, ML

Mol Cell Biol 2001
9372948 Architecture of the yeast origin recognition complex bound to origins of DNA replication.

Lee, DG, Bell, SP

Mol Cell Biol 1997
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Orthologous Events
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