Reactome | Activation of the pre-replicative complex

Activation of the pre-replicative complex

Stable Identifier

R-HSA-68962

Type

Pathway

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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Activation of the pre-replicative complex

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In S. cerevisiae, two ORC subunits, Orc1 and Orc5, both bind ATP, and Orc1 in addition has ATPase activity. Both ATP binding and ATP hydrolysis appear to be essential functions in vivo. ATP binding by Orc1 is unaffected by the association of ORC with origin DNA (ARS) sequences, but ATP hydrolysis is ARS-dependent, being suppressed by associated double-stranded DNA and stimulated by associated single-stranded DNA. These data are consistent with the hypothesis that ORC functions as an ATPase switch, hydrolyzing bound ATP and changing state as DNA unwinds at the origin immediately before replication. It is attractive to speculate that ORC likewise functions as a switch as human pre-replicative complexes are activated, but human Orc proteins are not well enough characterized to allow the model to be critically tested. mRNAs encoding human orthologs of all six Orc proteins have been cloned, and ATP-binding amino acid sequence motifs have been identified in Orc1, Orc4, and Orc5. Interactions among proteins expressed from the cloned genes have been characterized, but the ATP-binding and hydrolyzing properties of these proteins and complexes of them have not been determined.

Literature References

PubMed ID	Title	Journal	Year
11323433	Assembly of the human origin recognition complex. Vashee, S, Kelly, TJ, Simancek, P, Challberg, MD	J Biol Chem	2001
9765232	ORC5L, a new member of the human origin recognition complex, is deleted in uterine leiomyomas and malignant myeloid diseases. Thome, KC, Hou, ZH, Quintana, DG, Dutta, A, Ligon, AH, Morton, CC	J Biol Chem	1998
11395502	Architecture of the human origin recognition complex. Delmolino, L, Dutta, A, Dhar, SK	J Biol Chem	2001
10402192	latheo encodes a subunit of the origin recognition complex and disrupts neuronal proliferation and adult olfactory memory when mutant. Lane, WS, Tully, T, Hou, ZH, Jones, CJ, Velinzon, K, Quintana, DG, Mihalek, RM, Boynton, S, Pinto, S, Dutta, A, Smith, P, Wohlschlegel, JA, Austin, RJ, Hendricks, M	Neuron	1999
10801458	ATPase switches controlling DNA replication initiation. Bell, SP, Lee, DG	Curr Opin Cell Biol	2000
11779870	Nuclear organization of DNA replication initiation proteins in mammalian cells. Ishimi, Y, Tsurumi, T, Nakamura, H, Kiyono, T, Fujita, M	J Biol Chem	2002
7502077	Conserved initiator proteins in eukaryotes. Hidaka, M, Gavin, KA, Stillman, B	Science	1996
10970868	Regulation of origin recognition complex conformation and ATPase activity: differential effects of single-stranded and double-stranded DNA binding. Bell, SP, Makhov, AM, Klemm, RD, Lee, DG	EMBO J	2000
9353276	Identification of HsORC4, a member of the human origin of replication recognition complex. Thome, KC, Hou, Zh, Saha, P, Quintana, DG, Dutta, A, Hendricks, M	J Biol Chem	1997
12169736	Orc6 involved in DNA replication, chromosome segregation, and cytokinesis. Stillman, B, Prasanth, SG, Prasanth, KV	Science	2002
11459976	ATP bound to the origin recognition complex is important for preRC formation. Bell, SP, Klemm, RD	Proc Natl Acad Sci U S A	2001
9038340	Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex. Bell, SP, Austin, RJ, Klemm, RD	Cell	1997
9829972	The Orc4p and Orc5p subunits of the Xenopus and human origin recognition complex are related to Orc1p and Cdc6p. Zou-Yang, XH, Stillman, B, Gavin, K, Kobayashi, R, Hunt, T, Pappin, D, Canas, B, Tugal, T	J Biol Chem	1999