DNA replication in eukaryotes results from a highly coordinated interaction between proteins, often as part of protein complexes, and the DNA template. One of the key early steps leading to DNA replication is formation of the pre-replication complex, or pre-RC. The pre-RC is formed by the sequential binding of the origin recognition complex (ORC), Cdc6 and Cdt1 proteins, and the MCM complex. Activation of the pre-RC into the initiation complex (IC) is achieved via the action of S-phase kinases, eventually leading to the loading of the replication machinery.Recently, a novel replication complex, GINS (for Go, Ichi, Nii, and San; five, one, two, and three in Japanese), has been identified. The precise function of GINS is not known. However, genetic and two-hybrid interactions indicate that it mediates the loading of the enzymatic replication machinery at a step after the action of the S-phase kinases. Furthermore, GINS may be a part of the replication machinery itself, since it is found associated with replicating DNA. Electron microscopy of GINS shows that it forms a ring-like structure, reminiscent of the structure of PCNA, the DNA polymerase delta replication clamp.This observation, coupled with the observed interactions for GINS, indicates that the complex may represent the replication clamp for DNA polymerase epsilon.The GINS complex is essential for initiation of DNA replication in Xenopus egg extracts. This 100 kDa stable complex includes Sld5, Psf1, Psf2, and Psf3. Homologues of these components are found also in other eukaryotes. The archaeal GINS complex contains two subunits (SSO0772/gins23 and SO1049/gins15 in Sulfolobus) that are poorly conserved homologues of the eukaryotic GINS subunits. Only Gins23 is included in this entry.The eukaryotic GINS subunits are homologous. The four subunits of the complex consist of two domains each, termed the alpha-helical (A) and beta-strand (B) domains. The A and B domains of Sld5/Psf1 are permuted with respect to Psf1/Psf3.