Reactome | DNA Replication

DNA Replication

Stable Identifier

R-HSA-69306

Type

Pathway

Species

Homo sapiens

Compartment

nucleoplasm, cytosol

ReviewStatus

5/5

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DNA Replication (Homo sapiens)

General

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Studies in the past decade have suggested that the basic mechanism of DNA replication initiation is conserved in all kingdoms of life. Initiation in unicellular eukaryotes, in particular Saccharomyces cerevisiae (budding yeast), is well understood, and has served as a model for studies of DNA replication initiation in multicellular eukaryotes, including humans. In general terms, the first step of initiation is the binding of the replication initiator to the origin of replication. The replicative helicase is then assembled onto the origin, usually by a helicase assembly factor. Either shortly before or shortly after helicase assembly, some local unwinding of the origin of replication occurs in a region rich in adenine and thymine bases (often termed a DNA unwinding element, DUE). The unwound region provides the substrate for primer synthesis and initiation of DNA replication. The best-defined eukaryotic origins are those of S. cerevisiae, which have well-conserved sequence elements for initiator binding, DNA unwinding and binding of accessory proteins. In multicellular eukaryotes, unlike S. cerevisiae, these loci appear not to be defined by the presence of a DNA sequence motif. Indeed, choice of replication origins in a multicellular eukaryote may vary with developmental stage and tissue type. In cell-free models of metazoan DNA replication, such as the one provided by Xenopus egg extracts, there are only limited DNA sequence specificity requirements for replication initiation (Kelly & Brown 2000; Bell & Dutta 2002; Marahrens & Stillman 1992; Cimbora & Groudine 2001; Mahbubani et al 1992, Hyrien & Mechali 1993).

Literature References

PubMed ID	Title	Journal	Year
11257218	The control of mammalian DNA replication: a brief history of space and timing. Cimbora, DM, Groudine, M	Cell	2001
1579437	DNA replication initiates at multiple sites on plasmid DNA in Xenopus egg extracts. Mahbubani, HM, Paull, T, Elder, JK, Blow, JJ	Nucleic Acids Res	1992
8223461	Chromosomal replication initiates and terminates at random sequences but at regular intervals in the ribosomal DNA of Xenopus early embryos. Hyrien, O, Méchali, M	EMBO J	1993
12045100	DNA replication in eukaryotic cells. Bell, SP, Dutta, A	Annu Rev Biochem	2002
10966477	Regulation of chromosome replication. Kelly, TJ, Brown, GW	Annu Rev Biochem	2000
1536007	A yeast chromosomal origin of DNA replication defined by multiple functional elements. Marahrens, Y, Stillman, B	Science	1992