Stephen P. Bell, Karim Labib
Genetics July 1, 2016 vol. 203 no. 3 1027-1067
Abstract
The accurate and complete replication of genomic DNA is essential for all life. In eukaryotic cells, the assembly of the multi-enzyme replisomes that perform replication is divided into stages that occur at distinct phases of the cell cycle. Replicative DNA helicases are loaded around origins of DNA replication exclusively during G1 phase. The loaded helicases are then activated during S phase and associate with the replicative DNA polymerases and other accessory proteins. The function of the resulting replisomes is monitored by checkpoint proteins that protect arrested replisomes and inhibit new initiation when replication is inhibited. The replisome also coordinates nucleosome disassembly, assembly, and the establishment of sister chromatid cohesion. Finally, when two replisomes converge they are disassembled. Studies in Saccharomyces cerevisiae have led the way in our understanding of these processes. Here, we review our increasingly molecular understanding of these events and their regulation.
See: http://www.genetics.org/content/203/3/1027?etoc
Figure 4. Remodeling of the Mcm2-7 double hexamer and origin DNA during helicase activation. The loaded Mcm2-7 double hexamer encircles double-stranded origin DNA (top). In contrast, the active helicase (the Cdc45/Mcm2-7/GINS or CMG complex) contains one copy of the Mcm2-7 complex and encircles ssDNA (bottom). This transition requires dissolution of the interactions between the two Mcm2-7 hexamers, melting of the origin DNA, opening of each Mcm2-7 ring, extrusion of opposite ssDNAs from the two Mcm2-7 complexes, and reclosing of the Mcm2-7 rings. The relative order of these events during helicase activation is currently unknown.
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