The Origin Recognition Complex in Human Diseases

Overview

Journal Biosci Rep

Specialty Cell Biology

Date 2013 May 14

PMID 23662735

Citations 13

Authors

Zhen Shen

Affiliations

Soon will be listed here.

Abstract

ORC (origin recognition complex) serves as the initiator for the assembly of the pre-RC (pre-replication complex) and the subsequent DNA replication. Together with many of its non-replication functions, ORC is a pivotal regulator of various cellular processes. Notably, a number of reports connect ORC to numerous human diseases, including MGS (Meier-Gorlin syndrome), EBV (Epstein-Barr virus)-infected diseases, American trypanosomiasis and African trypanosomiasis. However, much of the underlying molecular mechanism remains unclear. In those genetic diseases, mutations in ORC alter its function and lead to the dysregulated phenotypes; whereas in some pathogen-induced symptoms, host ORC and archaeal-like ORC are exploited by these organisms to maintain their own genomes. In this review, I provide detailed examples of ORC-related human diseases, and summarize the current findings on how ORC is involved and/or dysregulated. I further discuss how these discoveries can be generalized as model systems, which can then be applied to elucidating other related diseases and revealing potential targets for developing effective therapies.

Citing Articles

Elevated origin recognition complex subunit 6 expression promotes non-small cell lung cancer cell growth.

Sang Y, Luo C, Huang B, Wu S, Shu J, Lan C Cell Death Dis. 2024; 15(9):700.

PMID: 39349930 PMC: 11442828. DOI: 10.1038/s41419-024-07081-y.

Origin recognition complex 6 overexpression promotes growth of glioma cells.

Yang W, Zhang W, Wang Y, Lou Y, Cai Y, Zhu J Cell Death Dis. 2024; 15(7):485.

PMID: 38971772 PMC: 11227543. DOI: 10.1038/s41419-024-06764-w.

Koch C, Prigge A, Setar L, Anekalla K, Do-Umehara H, Abdala-Valencia H Front Immunol. 2022; 13:924792.

PMID: 36211387 PMC: 9540395. DOI: 10.3389/fimmu.2022.924792.

Replication Stress, Genomic Instability, and Replication Timing: A Complex Relationship.

Briu L, Maric C, Cadoret J Int J Mol Sci. 2021; 22(9).

PMID: 33946274 PMC: 8125245. DOI: 10.3390/ijms22094764.

Transcriptomic profiling and genomic mutational analysis of Human coronavirus (HCoV)-229E -infected human cells.

Friedman N, Jacob-Hirsch J, Drori Y, Eran E, Kol N, Nayshool O PLoS One. 2021; 16(2):e0247128.

PMID: 33630927 PMC: 7906355. DOI: 10.1371/journal.pone.0247128.

References

Micklem G, Rowley A, Harwood J, Nasmyth K, Diffley J . Yeast origin recognition complex is involved in DNA replication and transcriptional silencing. Nature. 1993; 366(6450):87-9. DOI: 10.1038/366087a0. View

Chesnokov I, Remus D, Botchan M . Functional analysis of mutant and wild-type Drosophila origin recognition complex. Proc Natl Acad Sci U S A. 2001; 98(21):11997-2002. PMC: 59756. DOI: 10.1073/pnas.211342798. View

Prasanth S, Prasanth K, Siddiqui K, Spector D, Stillman B . Human Orc2 localizes to centrosomes, centromeres and heterochromatin during chromosome inheritance. EMBO J. 2004; 23(13):2651-63. PMC: 449767. DOI: 10.1038/sj.emboj.7600255. View

Norseen J, Thomae A, Sridharan V, Aiyar A, Schepers A, Lieberman P . RNA-dependent recruitment of the origin recognition complex. EMBO J. 2008; 27(22):3024-35. PMC: 2585170. DOI: 10.1038/emboj.2008.221. View

Ballestas M, Chatis P, Kaye K . Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen. Science. 1999; 284(5414):641-4. DOI: 10.1126/science.284.5414.641. View

Chuang R, Kelly T . The fission yeast homologue of Orc4p binds to replication origin DNA via multiple AT-hooks. Proc Natl Acad Sci U S A. 1999; 96(6):2656-61. PMC: 15824. DOI: 10.1073/pnas.96.6.2656. View

Barry J, McCulloch R . Antigenic variation in trypanosomes: enhanced phenotypic variation in a eukaryotic parasite. Adv Parasitol. 2001; 49:1-70. DOI: 10.1016/s0065-308x(01)49037-3. View

Rohrbough J, Pinto S, Mihalek R, Tully T, Broadie K . latheo, a Drosophila gene involved in learning, regulates functional synaptic plasticity. Neuron. 1999; 23(1):55-70. DOI: 10.1016/s0896-6273(00)80753-9. View

GORLIN R, cervenka J, Moller K, Horrobin M, WITKOP Jr C . Malformation syndromes. A selected miscellany. Birth Defects Orig Artic Ser. 1975; 11(2):39-50. View

10.

Beck D, Burton A, Oda H, Ziegler-Birling C, Torres-Padilla M, Reinberg D . The role of PR-Set7 in replication licensing depends on Suv4-20h. Genes Dev. 2012; 26(23):2580-9. PMC: 3521623. DOI: 10.1101/gad.195636.112. View

11.

Bicknell L, Walker S, Klingseisen A, Stiff T, Leitch A, Kerzendorfer C . Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome. Nat Genet. 2011; 43(4):350-5. DOI: 10.1038/ng.776. View

12.

Dorsett D . Cohesin: genomic insights into controlling gene transcription and development. Curr Opin Genet Dev. 2011; 21(2):199-206. PMC: 3070859. DOI: 10.1016/j.gde.2011.01.018. View

13.

Huang D, Fanti L, Pak D, Botchan M, Pimpinelli S, KELLUM R . Distinct cytoplasmic and nuclear fractions of Drosophila heterochromatin protein 1: their phosphorylation levels and associations with origin recognition complex proteins. J Cell Biol. 1998; 142(2):307-18. PMC: 2133057. DOI: 10.1083/jcb.142.2.307. View

14.

Dillin A, Rine J . Roles for ORC in M phase and S phase. Science. 1998; 279(5357):1733-7. DOI: 10.1126/science.279.5357.1733. View

15.

Tao Q, Young L, Woodman C, Murray P . Epstein-Barr virus (EBV) and its associated human cancers--genetics, epigenetics, pathobiology and novel therapeutics. Front Biosci. 2006; 11:2672-713. DOI: 10.2741/2000. View

16.

Iyer L, Leipe D, Koonin E, Aravind L . Evolutionary history and higher order classification of AAA+ ATPases. J Struct Biol. 2004; 146(1-2):11-31. DOI: 10.1016/j.jsb.2003.10.010. View

17.

Benmerzouga I, Concepcion-Acevedo J, Kim H, Vandoros A, Cross G, Klingbeil M . Trypanosoma brucei Orc1 is essential for nuclear DNA replication and affects both VSG silencing and VSG switching. Mol Microbiol. 2012; 87(1):196-210. PMC: 3535549. DOI: 10.1111/mmi.12093. View

18.

Norseen J, Johnson F, Lieberman P . Role for G-quadruplex RNA binding by Epstein-Barr virus nuclear antigen 1 in DNA replication and metaphase chromosome attachment. J Virol. 2009; 83(20):10336-46. PMC: 2753104. DOI: 10.1128/JVI.00747-09. View

19.

Ballestas M, Kaye K . Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 mediates episome persistence through cis-acting terminal repeat (TR) sequence and specifically binds TR DNA. J Virol. 2001; 75(7):3250-8. PMC: 114118. DOI: 10.1128/JVI.75.7.3250-3258.2001. View

20.

Chaudhuri B, Xu H, Todorov I, Dutta A, Yates J . Human DNA replication initiation factors, ORC and MCM, associate with oriP of Epstein-Barr virus. Proc Natl Acad Sci U S A. 2001; 98(18):10085-9. PMC: 56919. DOI: 10.1073/pnas.181347998. View