Anti-PSF1 (N-terminal) polyclonal antibody

High-fidelity chromosomal DNA replication is fundamental to all forms of cellular life and requires the complex interplay of a wide variety of essential and non-essential protein factors in a spatially and temporally co-ordinated manner. In eukaryotes, the GINS complex (from the Japanese go-ichi-ni-san meaning 5-1-2-3, after the four related subunits of the complex Sld5, Psf1, Psf2 and Psf3) was recently identified as a novel factor essential for both the initiation and elongation stages of the replication process. Biochemical analysis has placed GINS at the heart of the eukaryotic replication apparatus as a component of the CMG [Cdc45-MCM (minichromosome maintenance) helicase-GINS] complex that most likely serves as the replicative helicase, unwinding duplex DNA ahead of the moving replication fork. GINS homologues are found in the archaea and have been shown to interact directly with the MCM helicase and with primase, suggesting a central role for the complex in archaeal chromosome replication also. The present review summarizes Current knowledge of the Structure, function and evolution of the GINS complex in eukaryotes and archaea, discusses possible functions of the GINS complex and highlights recent results that point to possible regulation of GINS function in response to DNA damage.

SLD5 is a member of the GINS complex composed of PSF1, PSF2, PSF3 and SLD5, playing a critical role in the formation of the DNA replication fork with CDC45 in yeast. Previously, we had isolated a PSF1 orthologue from a murine hematopoietic stem cell DNA library and were then able to identify orthologues of all the other GINS members by the yeast two hybrid approach using PSF1 as the bait. These GINS orthologues may also function in DNA replication in mammalian cells because they form tetrameric complexes as observed in yeast, and gene deletion mutants of both PSF1 and SLD5 result in a lack of epiblast proliferation and early embryonic lethality. However, we found that PSF1 is also involved in chromosomal segregation in M phase, consistent with recent suggestions that homologues of genes associated with DNA replication in lower organisms also regulate cellular events other than DNA replication in mammalian cells. Here we analyzed the function of SLD5 other than DNA replication and found that it is active in DNA damage and repair. Attenuation of SLD5 expression results in marked DNA damage in both normal cells and cancer cells, suggesting that it protects against DNA damage. Attenuation of SLD5 delays the DNA repair response and cell cycle restoration in normal cells but not in cancer cells. These findings suggest that SLD5 might represent a therapeutic target molecule acting at the level of tumor stromal cells rather than the cancerous cells themselves, because development of the tumor microenvironment could be delayed or disrupted by the suppression of its expression in the normal cell types within the tumor.