DOI: 10.1046/j.1365-2443.2002.00544.x. Control of DNA replication licensing in a cell cycle

Control of DNA replication licensing in a cell cycle

10.1046/j.1365-2443.2002.00544.x

Crossref journal-article

Wiley

Genes to Cells (311)

Abstract

To maintain genome integrity in eukaryotes, DNA must be duplicated precisely once before cell division occurs. A process called replication licensing ensures that chromosomes are replicated only once per cell cycle. Its control has been uncovered by the discovery of the CDKs (cyclin dependent kinases) as master regulators of the cell cycle and the initiator proteins of DNA replication, such as the Origin Recognition Complex (ORC), Cdc6/18, Cdt1 and the MCM complex. At the end of mitosis, the MCM complex is loaded on to chromatin with the aid of ORC, Cdc6/18 and Cdt1, and chromatin becomes licensed for replication. CDKs, together with the Cdc7 kinase, trigger the initiation of replication, recruiting the DNA replicating enzymes on sites of replication. The activated MCM complex appears to play a key role in the DNA unwinding step, acting as a replicating helicase and moves along with the replication fork, at the same time bringing the origins to the unlicensed state. The cycling of CDK activity in the cell cycle separates the two states of replication origins, the licensed state in G1‐phase and the unlicensed state for the rest of the cell cycle. Only when CDK drops at the completion of mitosis, is the restriction on licensing relieved and a new round of replication is allowed. Such a CDK‐regulated licensing control is conserved from yeast to higher eukaryotes, and ensures that DNA replication takes place only once in a cycle. Xenopus laevis and mammalian cells have an additional system to control licensing. Geminin, whose degradation at the end of mitosis is essential for a new round of licensing, has been shown to bind Cdt1 and negatively regulate it, providing a new insight into the regulation of DNA replication in higher eukaryotes.

Bibliography

Nishitani, H., & Lygerou, Z. (2002). Control of DNA replication licensing in a cell cycle. Genes to Cells, 7(6), 523â534. Portico.

Authors 2

Hideo Nishitani (first)
Zoi Lygerou (additional)

References 101 Referenced 185

Dates

Type	When
Created	22 years, 5 months ago (March 11, 2003, 5:49 p.m.)
Deposited	1 year, 9 months ago (Oct. 30, 2023, 10:25 p.m.)
Indexed	1 month, 1 week ago (July 16, 2025, 9:50 a.m.)
Issued	23 years, 2 months ago (June 1, 2002)
Published	23 years, 2 months ago (June 1, 2002)
Published Online	23 years, 2 months ago (June 6, 2002)
Published Print	23 years, 2 months ago (June 1, 2002)

Funders 0

None

BibTeX

@article{Nishitani_2002, title={Control of DNA replication licensing in a cell cycle}, volume={7}, ISSN={1365-2443}, url={http://dx.doi.org/10.1046/j.1365-2443.2002.00544.x}, DOI={10.1046/j.1365-2443.2002.00544.x}, number={6}, journal={Genes to Cells}, publisher={Wiley}, author={Nishitani, Hideo and Lygerou, Zoi}, year={2002}, month=jun, pages={523–534} }

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