D
IPR032705

Origin recognition complex subunit 4, C-terminal

InterPro entry
Short nameORC4_C

Description

This entry represents the C terminus of origin recognition complex subunit 4
[2, 18]
.

The Origin Recognition Complex (ORC) is a six-subunit ATP-dependent DNA-binding complex encoded by ORC1-6
[1]
. ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle
[6]
. ORC directs DNA replication throughout the genome and is required for its initiation
[9, 8, 11]
. ORC bound at replication origins serves as the foundation for assembly of the pre-replicative complex (pre-RC), which includes Cdc6, Tah11 (aka Cdt1), and the Mcm2-7 complex
[10, 13, 12, 19]
. Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase
[15, 14, 7]
. Cell cycle-regulated phosphorylation of ORC2, ORC6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates initiation of DNA replication, including blocking reinitiation in G2/M phase
[6, 16, 17, 5]
.

In yeast, ORC also plays a role in the establishment of silencing at the mating-type loci Hidden MAT Left (HML) and Hidden MAT Right (HMR)
[9, 8, 11]
. ORC participates in the assembly of transcriptionally silent chromatin at HML and HMR by recruiting the Sir1 silencing protein to the HML and HMR silencers
[11, 4, 3]
.

References

1.Multiple functions of the origin recognition complex. Chesnokov IN. Int. Rev. Cytol. 256, 69-109, (2007). View articlePMID: 17241905

2.Identification of HsORC4, a member of the human origin of replication recognition complex. Quintana DG, Hou Zh, Thome KC, Hendricks M, Saha P, Dutta A. J. Biol. Chem. 272, 28247-51, (1997). View articlePMID: 9353276

3.The origin recognition complex, SIR1, and the S phase requirement for silencing. Fox CA, Ehrenhofer-Murray AE, Loo S, Rine J. Science 276, 1547-51, (1997). View articlePMID: 9171055

4.Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing. Triolo T, Sternglanz R. Nature 381, 251-3, (1996). View articlePMID: 8622770

5.Disruption of mechanisms that prevent rereplication triggers a DNA damage response. Archambault V, Ikui AE, Drapkin BJ, Cross FR. Mol. Cell. Biol. 25, 6707-21, (2005). View articlePMID: 16024805

6.Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins. Matsuda K, Makise M, Sueyasu Y, Takehara M, Asano T, Mizushima T. FEMS Yeast Res. 7, 1263-9, (2007). PMID: 17825065

7.Origin recognition and the chromosome cycle. Stillman B. FEBS Lett. 579, 877-84, (2005). View articlePMID: 15680967

8.The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing. Bell SP, Mitchell J, Leber J, Kobayashi R, Stillman B. Cell 83, 563-8, (1995). View articlePMID: 7585959

9.ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex. Bell SP, Stillman B. Nature 357, 128-34, (1992). View articlePMID: 1579162

10.The origin recognition complex interacts with a bipartite DNA binding site within yeast replicators. Rao H, Stillman B. Proc. Natl. Acad. Sci. U.S.A. 92, 2224-8, (1995). View articlePMID: 7892251

11.Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae. Gibson DG, Bell SP, Aparicio OM. Genes Cells 11, 557-73, (2006). View articlePMID: 16716188

12.ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA. Speck C, Chen Z, Li H, Stillman B. Nat. Struct. Mol. Biol. 12, 965-71, (2005). View articlePMID: 16228006

13.Initiation complex assembly at budding yeast replication origins begins with the recognition of a bipartite sequence by limiting amounts of the initiator, ORC. Rowley A, Cocker JH, Harwood J, Diffley JF. EMBO J. 14, 2631-41, (1995). PMID: 7781615

14.DNA replication in eukaryotic cells. Bell SP, Dutta A. Annu. Rev. Biochem. 71, 333-74, (2002). View articlePMID: 12045100

15.Regulation of chromosome replication. Kelly TJ, Brown GW. Annu. Rev. Biochem. 69, 829-80, (2000). View articlePMID: 10966477

16.Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle. Weinreich M, Liang C, Chen HH, Stillman B. Proc. Natl. Acad. Sci. U.S.A. 98, 11211-7, (2001). View articlePMID: 11572976

17.Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nguyen VQ, Co C, Li JJ. Nature 411, 1068-73, (2001). View articlePMID: 11429609

18.The fission yeast homologue of Orc4p binds to replication origin DNA via multiple AT-hooks. Chuang RY, Kelly TJ. Proc. Natl. Acad. Sci. U.S.A. 96, 2656-61, (1999). View articlePMID: 10077566

19.Structural mechanism for replication origin binding and remodeling by a metazoan origin recognition complex and its co-loader Cdc6. Schmidt JM, Bleichert F. Nat Commun 11, 4263, (2020). PMID: 32848132

Further reading

20. An essential role for Orc6 in DNA replication through maintenance of pre-replicative complexes. Semple JW, Da-Silva LF, Jervis EJ, Ah-Kee J, Al-Attar H, Kummer L, Heikkila JJ, Pasero P, Duncker BP. EMBO J. 25, 5150-8, (2006). View articlePMID: 17053779

21. Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase. Randell JC, Bowers JL, Rodriguez HK, Bell SP. Mol. Cell 21, 29-39, (2006). View articlePMID: 16387651

22. ATP hydrolysis by ORC catalyzes reiterative Mcm2-7 assembly at a defined origin of replication. Bowers JL, Randell JC, Chen S, Bell SP. Mol. Cell 16, 967-78, (2004). View articlePMID: 15610739

23. ATP bound to the origin recognition complex is important for preRC formation. Klemm RD, Bell SP. Proc. Natl. Acad. Sci. U.S.A. 98, 8361-7, (2001). View articlePMID: 11459976

24. Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex. Klemm RD, Austin RJ, Bell SP. Cell 88, 493-502, (1997). View articlePMID: 9038340

25. Initiation of DNA replication in eukaryotic cells. Dutta A, Bell SP. Annu. Rev. Cell Dev. Biol. 13, 293-332, (1997). View articlePMID: 9442876

26. The ORC ubiquitin ligase OBI1 promotes DNA replication origin firing. Coulombe P, Nassar J, Peiffer I, Stanojcic S, Sterkers Y, Delamarre A, Bocquet S, Mechali M. Nat Commun 10, 2426, (2019). PMID: 31160578

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