IMR Press / FBL / Volume 4 / Issue 4 / DOI: 10.2741/fujita

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Cell cycle regulation of DNA replication initiation proteins in mammalian cells
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1 Masatoshi Fujita, Laboratory of Viral Oncology, Research Institute, Aichi Cancer Center, Kanokoden 1-1, Chikusa-ku, Nagoya 464-8681, Japan
Academic Editor:Hisao Masai
Front. Biosci. (Landmark Ed) 1999, 4(4), 816–823; https://doi.org/10.2741/fujita
Published: 1 December 1999
(This article belongs to the Special Issue DNA replication mechanisms and regulation)
Abstract

Genomic DNA has to be replicated completely and only once during a single cell cycle in order to maintain integrity. Eukaryotes have developed highly regulated machinery for precisely replicating genomic DNA that is fragmented into multiple chromosomes. Our knowledge of such mechanisms largely depends on findings with budding yeast, since identification of specific DNA sequences acting as replication origins, autonomously replicating sequences, has allowed extensive analyses of the initiation of DNA replication. Several factors essential for regulation of initiation have been identified, including ORC, CDC6 and MCM. Subsequent work has suggested that the fundamental machinery for DNA replication may be conserved in metazoan embryonic cells in which replication occurs sequence-independently, and also in mammalian nonembryonic cells, where replication origins are more specific. However, there are specific differences. In this review, information on function and regulation of mammalian initiation factors, ORC, CDC6 and MCM, is summarized, and yeast and embryonic systems are compared. A hypothetical model for the state of prereplication chromatin in mammalian cell nuclei and regulation during the cell cycle is also proposed.

Keywords
DNA replication
mammalian cell
initiation factor
ORC
CDC6
MCM
CDK
Review
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