DNA Replication


Deoxyribonucleic acid replication is the process leading to the duplication of genetic material in an organism.

Keywords: DNA replication; replication origin; origin structure; initiator protein; cruciform

Figure 1.

The principal elements of eukaryotic deoxyribonucleic acid (DNA) replication origins (ori). The minimal ori or ‘core’ element consists of: a DNA unwinding element (DUE) that is easily unwound; an origin recognition element (ORE), which is bound by the initiator protein(s) (IPs), including the Ku protein; an AT‐rich sequence (AT), where DNA bending occurs and an inverted repeat (IR) sequence that has the potential of extruding into a cruciform conformation and as such is bound by a cruciform‐binding protein (CBP), which in human cells was identified as belonging to the 14‐3‐3 protein family. The position of the AT and DUE elements with respect to ORE and IR elements indicates only their inclusion within a predicted core. The core element is flanked by the auxiliary components (Aux), which are binding sites of transcription factors that are specific to particular replication systems and influence the initiation of DNA replication, through their interaction with origin‐binding proteins and other replication proteins. (Adapted from DePamphilis ML (1993) Annual Review of Biochemistry 62: 29–63, and based on data regarding mammalian replication oris, described by Novac et al., ).



Bürkstümmer T, Bennett KL, Preradovic A et al. (2006) An efficient tandem affinity purification procedure for interaction proteomics in mammalian cells. Nature Methods 3: 1013–1019.

Dhar SK, Yoshida K, Machida Y et al. (2001) Replication from oriP of Epstein–Barr virus requires human ORC and is inhibited by Geminin. Cell 106: 287–296.

Di Paola D, Price GB and Zannis‐Hadjopoulos M (2006) Differrentially active origins of DNA replication in tumor versus normal cells. Cancer Research 66: 5094–5103.

Jacob F, Brenner S and Cuzin F (1963) On the regulation of DNA replication in bacteria. Cold Spring Harbor Symposium 28: 329–348.

Kamath S and Leffak M (2001) Multiple sites of replication initiation in the human β‐globin gene locus. Nucleic Acids Research 29: 1–9.

Lebofsky R, Heilig R, Sonnleitner M, Weissenbach J and Bensimon A (2006) DNA replication origin interference increases the spacing between initiation events in human cells. Molecular Biology of the Cell 17: 5337–5345.

Li C‐J, Bogan JA, Natale DA and DePamphilis ML (2000) Selective activation of pre‐replication complexes in vitro at specific sites in mammalian nuclei. Journal of Cell Science 113: 887–898.

Li CJ and DePamphilis ML (2002) Mammalian Orc1 protein is selectively released from chromatin and ubiquitinated during the S‐to‐M transition in the cell division cycle. Molecular and Cellular Biology 22: 105–116.

Li G, Nelsen C and Hendrickson EA (2002) Ku86 is essential in human somatic cells. Proceedings of the National Academy of Sciences of the USA 99: 832–837.

Natale DA, Li C‐J, Sun W‐H and DePamphilis ML (2000) Selective instability of Orc1 protein accounts for the absence of functional origin recognition complexes during the M–G1 transition in mammals. The EMBO Journal 19: 2728–2738.

Norio P and Schildkraut CL (2001) Visualization of DNA replication on individual Epstein–Barr virus episomes. Science 294: 2361–2364.

Novac O, Alvarez D, Pearson CE, Price GB and Zannis‐Hadjopoulos M (2002) The human cruciform‐binding protein, CBP, is involved in DNA replication and associates in vivo with mammalian replication origins. Journal of Biological Chemistry 277: 11174–11183.

Novac O, Matheos D, Araujo FD, Price GB and Zannis‐Hadjopoulos M (2001) In vivo association of Ku with mammalian origins of DNA replication. Molecular Biology of the Cell 12: 3386–3401.

Nussenzweig A, Chen CH, Soares VD et al. (1996) Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature 382: 551–555.

Price GB, Allarakhia M, Cossons N et al. (2003) A human consensus sequence capable of autonomous DNA replication for development of human gene delivery systems. Journal of Biological Chemistry 278: 19649–19659.

Raghuraman MK, Winzeler EA, Collingwood D et al. (2001) Replication dynamics of the yeast genome. Science 294: 115–121.

Saitoh Y, Miyagi S, Ariga H and Tsutsumi K‐I (2002) Functional domains involved in the interaction between Orc1 and transcriptional repressor AIF‐C that bind to an origin/promoter of the rat aldolase B gene. Nucleic Acids Research 30: 5205–5212.

Schild‐Poulter C, Matheos D, Novac O et al. (2003) Differential DNA binding of Ku antigen determines its involvement in DNA replication. DNA and Cell Biology 22: 65–78.

Schwob E (2004) Flexibility and governance in eukaryotic DNA replications. Current Opinion in Microbiology 7: 680–690.

Sibani S, Price GB and Zannis‐Hadjopoulos M (2005) Ku80 binds to human replication origins prior to the assembly of the ORC complex. Biochemistry 44(21): 7885–7896.

Stillman B (2001) Genomic views of genome duplication. Science 294: 2301–2304.

Takebayashi S‐I, Manders EMM, Kimura H, Taguchi H and Okumura K (2001) Mapping sites where replication initiates in mammalian cells using DNA fibers. Experimental Cell Research 271: 263–268.

Wyrick JJ, Aparicio JG, Chen T et al. (2001) Genome‐wide distribution of ORC and MCM proteins in S. cerevisiae: high‐resolution mapping of replication origins. Science 294: 2357–2360.

Yahyaoui W, Callejo M, Price GB and Zannis‐Hadjopoulos M (2007) Deletion of the cruciform binding domain in CBP/14‐3‐3 displays reduced origin binding and initiation of DNA replication in budding yeast. BMC Molecular Biology 8: 27.

Zannis‐Hadjopoulos M, Sibani S and Price GB (2004) Replication origin binding proteins. Frontiers in Bioscience 9: 2133–2143.

Further Reading

DePamphilis ML (1999) Replication origins in metazoan chromosomes: fact or fiction? BioEssays 21: 5–16.

Kelly TJ and Brown GW (2000) Regulation of chromosome replication. Annual Review of Biochemistry 69: 829–880.

Malkas LH (1998) DNA replication machinery of the mammalian cell. Journal of Cellular Biochemistry 30: 18–29.

Méchali M (2001) DNA replication origins: from sequence specificity to epigenetics. Nature Reviews. Genetics 2: 640–645.

Pearson CE, Zorbas H, Price GB and Zannis‐Hadjopoulos M (1996) Inverted repeats, stem‐loops, and cruciforms: significance for initiation of DNA replication. Journal of Cellular Biochemistry 63: 1–22.

Quintana DG and Dutta A (1999) The metazoan origin recognition complex. Frontiers in Bioscience 4: 805–815.

Stillman B (1996) Comparison of DNA replication in cells from Prokarya and Eukarya. In: DePamphilis ML (ed.) DNA Replication in Eukaryotic Cells. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

Tuteja R and Tuteja N (2000) Ku autoantigen: a multifunctional DNA‐binding protein. Critical Reviews in Biochemistry and Molecular Biology 35: 1–33.

Zannis‐Hadjopoulos M and Price GB (1998) Regulatory parameters of DNA replication. Critical Reviews in Eukaryotic Gene Expression 8: 81–106.

Zannis‐Hadjopoulos M and Price GB (1999) Eukaryotic DNA replication. Journal of Cellular Biochemistry Supplements 32: 1–14.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Zannis‐Hadjopoulos, Maria(Dec 2007) DNA Replication. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005282.pub2]