Eukaryotic Chromosome DNA Replication: Where, When, and How?

Abstract

DNA replication is central to cell proliferation. Studies in the past six decades since the proposal of a semiconservative mode of DNA replication have confirmed the high degree of conservation of the basic machinery of DNA replication from prokaryotes to eukaryotes. However, the need for replication of a substantially longer segment of DNA in coordination with various internal and external signals in eukaryotic cells has led to more complex and versatile regulatory strategies. The replication program in higher eukaryotes is under a dynamic and plastic regulation within a single cell, or within the cell population, or during development. We review here various regulatory mechanisms that control the replication program in eukaryotes and discuss future directions in this dynamic field.

Genomic Analysis of the DNA Replication Timing Program during Mitotic S Phase in Maize (Zea mays) Root Tips

“…During each S phase, there must be a complete and accurate duplication of the genome, which must occur in a regulated and reproducible way from one cell cycle to the next (Klein and Gilbert, 2016). To accomplish this task, higher eukaryotes organize the process both temporally and spatially so that replication initiates at multiple loci, or origins, distributed throughout the genome, with different origins becoming active at different times during S phase (Masai et al, 2010). In most higher eukaryotes, there is an association between early replication and euchromatic, transcriptionally active chromatin (Hatton et al, 1988;Hiratani et al, 2008;Lee et al, 2010;Ryba et al, 2010), though there are classes of genes that have a much weaker association with replication time and are developmentally regulated in humans and mice (Hiratani et al, 2008;Rivera-Mulia et al, 2015).…”

“Reductional anaphase” in replication-defective cells is caused by ubiquitin-conjugating enzyme Cdc34-mediated deregulation of the spindle

“…2,3 Another surveillance mechanism, the spindle complex). [19][20][21] Although yeast cells deficient in Cdc6 function are unable to initiate DNA replication, they proceed to segregate the unreplicated chromosomes unequally between the mother and daughter compartments. 17 This abnormal segregation, termed "reductional anaphase," is thought to be due to cells' premature entry into mitosis because of its striking resemblance to sisterchromatid segregation during anaphase.…”

Building up the machinery for DNA replication

“…Like many other chromosome reactions, DNA replication depends on sequential assembly of factors that ultimately constitute machinery, termed replisome, capable of continuously unwinding duplex DNA and synthesising DNA chains on both strands. 1 The factors participating in eukaryotic DNA replication are surprisingly conserved from yeasts to human. The initial event for DNA replication is assembly of pre-RC (pre-Replicative Complex) composed of ORC, MCM and other accessory factors during G1 phase of cell cycle.…”