Editing S phase (section)

==DNA replication==
{{Main|DNA replication}}
[[File:Steps in DNA synthesis.svg|thumb|Steps in DNA synthesis]]

Throughout M phase and G1 phase, cells assemble inactive [[pre-replication complex]]es (pre-RC) on [[Origin of replication|replication origins]] distributed throughout the genome.<ref name=":2">{{cite journal | vauthors = Takeda DY, Dutta A | title = DNA replication and progression through S phase | journal = Oncogene | volume = 24 | issue = 17 | pages = 2827–43 | date = April 2005 | pmid = 15838518 | doi = 10.1038/sj.onc.1208616 | doi-access = free }}</ref> During S-phase, the cell converts pre-RCs into active replication forks to initiate DNA replication.<ref name=":2" /> This process depends on the kinase activity of [[Cell division cycle 7-related protein kinase|Cdc7]] and various S-phase CDKs, both of which are upregulated upon S-phase entry.<ref name=":2" />

Activation of the pre-RC is a closely regulated and highly sequential process. After Cdc7 and S-phase CDKs phosphorylate their respective substrates, a second set of replicative factors associate with the pre-RC.<ref name=":2" /> Stable association encourages [[Minichromosome maintenance|MCM helicase]] to unwind a small stretch of parental DNA into two strands of ssDNA, which in turn recruits replication protein A ([[Replication protein A|RPA]]), an ssDNA binding protein.<ref name=":2" /> RPA recruitment primes the replication fork for loading of replicative DNA [[DNA polymerase|polymerases]] and [[Proliferating cell nuclear antigen|PCNA]] sliding clamps.<ref name=":2" /> Loading of these factors completes the active replication fork and initiates synthesis of new DNA.

Complete replication fork assembly and activation only occurs on a small subset of replication origins. All eukaryotes possess many more replication origins than strictly needed during one cycle of DNA replication.<ref name=":3">{{cite journal | vauthors = Leonard AC, Méchali M | title = DNA replication origins | journal = Cold Spring Harbor Perspectives in Biology | volume = 5 | issue = 10 | pages = a010116 | date = October 2013 | pmid = 23838439 | pmc = 3783049 | doi = 10.1101/cshperspect.a010116 }}</ref> Redundant origins may increase the flexibility of DNA replication, allowing cells to control the rate of DNA synthesis and respond to replication stress.<ref name=":3" />