Noc3p (nucleolar complex-associated protein) is highly conserved in eukaryotes, and it plays a critical role in the initiation of DNA replication in budding yeast. Noc3p interacts with ORC and MCM proteins and serves as an important link between ORC and other initiation proteins to facilitate the chromatin association of Cdc6 and MCM proteins. On the other hand, a Noc complex including Noc3p is specifically involved in the formation and nuclear export of the ribosomal 40S subunit.

FAD24 (Factor for Adipocyte Differentiation) is the human homolog of Noc3p. It has been reported that hNOC3 is required for the regulation of DNA replication in cell proliferation as well as associated with cancer risk in the Chinese population. Overexpression of hNOC3 causes hyperplasia in adipose tissue an...[ Read more ]

Noc3p (nucleolar complex-associated protein) is highly conserved in eukaryotes, and it plays a critical role in the initiation of DNA replication in budding yeast. Noc3p interacts with ORC and MCM proteins and serves as an important link between ORC and other initiation proteins to facilitate the chromatin association of Cdc6 and MCM proteins. On the other hand, a Noc complex including Noc3p is specifically involved in the formation and nuclear export of the ribosomal 40S subunit.

FAD24 (Factor for Adipocyte Differentiation) is the human homolog of Noc3p. It has been reported that hNOC3 is required for the regulation of DNA replication in cell proliferation as well as associated with cancer risk in the Chinese population. Overexpression of hNOC3 causes hyperplasia in adipose tissue and improves glucose metabolism. Our data show that knockdown of hNOC3 in HeLa cells leads to significant defects in the chromatin association of the other pre-replicative complex proteins including hMCM proteins and hCdc6, as well as a severe delay in the entry of S phase and apoptosis. In addition, hNOC3 binds to chromatin throughout the cell cycle and interacts with hORC and hMCM proteins, shown by the results of chromatin binding assay and yeast two-hybrid assay. Recent investigation of ChlP assay for hNOC3 on its binding to specific genomic regions reveal that hNOC3 associates with multiple well-known human replication origins. These data strongly suggest that hNOC3 plays an important role in the initiation of DNA replication, just as its yeast homolog.