InterPro domain: IPR021151

The GINS complex is essential for initiation of DNA replication in Xenopus egg extracts [ 1 ]. This 100kDa stable complex includes Sld5, Psf1, Psf2, and Psf3. Homologues of these components are found also in other eukaryotes [ 2 ]. The archaeal GINS complex contains two subunits (SSO0772/gins23 and SO1049/gins15 in Sulfolobus) that are poorly conserved homologues of the eukaryotic GINS subunits [ 3 ]. 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 [ 4 ].

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 [ 5 , 5 ]. 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 [ 5 ]. Furthermore, GINS may be a part of the replication machinery itself, since it is found associated with replicating DNA [ 5 , 5 ]. Electron microscopy of GINS shows that it forms a ring-like structure [ 5 ], reminiscent of the structure of PCNA [ 5 ], 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 [ 6 ].

1. A novel ring-like complex of Xenopus proteins essential for the initiation of DNA replication. Genes Dev. 17, 1141-52
2. GINS, a novel multiprotein complex required for chromosomal DNA replication in budding yeast. Genes Dev. 17, 1153-65
3. GINS, a central nexus in the archaeal DNA replication fork. EMBO Rep. 7, 539-45
4. Structure of the human GINS complex and its assembly and functional interface in replication initiation. Nat. Struct. Mol. Biol. 14, 388-96
5. Crystal structure of the eukaryotic DNA polymerase processivity factor PCNA. Cell 79, 1233-43