SPhase

S phase, or synthesis phase, is the portion of the cell cycle during which the cell duplicates its DNA. In eukaryotic cells it follows G1 and precedes G2, forming the main part of interphase. S phase begins with the licensing of replication origins in G1, proceeds through the firing of origins and bidirectional replication forks, and ends when all chromosomes have been replicated, allowing the cell to enter G2.

DNA replication during S phase is semi-conservative and occurs at multiple origins arranged across the genome. Licensing involves the origin recognition complex (ORC) together with Cdc6 and Cdt1 loading the MCM2-7 helicase complex in G1. Activation by S-phase kinases such as CDK2–Cyclin E/A and DDK converts licensed origins into active forks. The helicase unwinds DNA while DNA polymerases synthesize new strands: leading-strand synthesis by one polymerase and lagging-strand synthesis by another in short fragments. Primase-Pol α embryos primers for Okazaki fragments on the lagging strand; primers are removed and replaced, and fragments are ligated. Nucleosome assembly behind the fork restores chromatin structure with the help of histone chaperones.

The timing of S phase is regulated by a replication timing program, with gene-rich regions often replicated early and heterochromatin replicated later. Checkpoints monitor replication and damage; stalled forks trigger ATR-CHK1–mediated responses to slow or pause progression and promote repair, while excessive DNA damage can activate ATM-CHK2 and arrest the cycle.

Duration varies by organism and cell type, typically lasting several hours in proliferating human cells. Completion of DNA replication is required before mitosis, and defects can lead to cell cycle arrest or apoptosis. Some chemotherapeutic agents specifically target DNA replication during S phase.