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 [1, 2]. 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 [3]. Furthermore, GINS may be a part of the replication machinery itself, since it is found associated with replicating DNA [3, 3]. Electron microscopy of GINS shows that it forms a ring-like structure [3], reminiscent of the structure of PCNA [3], 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 [4].

The GINS complex is essential for initiation of DNA replication in Xenopus egg extracts [4]. This 100 kDa stable complex includes Sld5, Psf1, Psf2, and Psf3. Homologues of these components are found also in other eukaryotes.

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. Crystal structure of the eukaryotic DNA polymerase processivity factor PCNA. Cell 79, 1233-43

DNA replication in eukaryotes results from a highly coordinated interaction between proteins, oft
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