Noc3 (Nucleolar complex associated protein) was originally identified by a genetic screen in budding yeast Saccharomyces cerevisiae. It was reported that it plays crucial roles in both ribosome biogenesis and DNA replication initiation. Its role in such important fundamental processes makes it essential for cell viability. It was shown to be needed for the maturation and nuclear export of the 40S subunit of ribosome. It also interacts with multiple replication initiation proteins including ORC (Origin recognition complex) and MCM (Minichromosome maintenance) and serves as an important bridge to facilitate the recruitment of Cdc6 (Cell division cycle) and Cdt1-MCM (Cdc10 dependent transcript) in pre-RC (Pre-replicative complex) assembly.

Mainly by sequence homology, FAD24 (Factor fo...[ Read more ]

Noc3 (Nucleolar complex associated protein) was originally identified by a genetic screen in budding yeast Saccharomyces cerevisiae. It was reported that it plays crucial roles in both ribosome biogenesis and DNA replication initiation. Its role in such important fundamental processes makes it essential for cell viability. It was shown to be needed for the maturation and nuclear export of the 40S subunit of ribosome. It also interacts with multiple replication initiation proteins including ORC (Origin recognition complex) and MCM (Minichromosome maintenance) and serves as an important bridge to facilitate the recruitment of Cdc6 (Cell division cycle) and Cdt1-MCM (Cdc10 dependent transcript) in pre-RC (Pre-replicative complex) assembly.

Mainly by sequence homology, FAD24 (Factor for adipocyte differentiation, noted as NOC3 in this thesis) was identified as the human homolog of Noc3. It was shown that FAD24 is needed in the process of clonal expansion before differentiation occurs. Our data suggest that, NOC3 in human cells not only regulates adipocyte differentiation, but it is also a very important member of the pre-RC. A series of experiments have been performed and results suggest that NOC3 associates with chromatin, particularly replication origins, throughout the cell cycle; Knockdown of NOC3 abrogates pre-RC assembly, hence inhibiting DNA replication initiation and S-phase entry; Depletion of NOC3 leads to apoptosis before the cells can enter S-phase; NOC3 physically interacts with multiple subunits of both ORC and MCM. These all together strongly support our hypothesis that, NOC3 is one of the pre-RC members in human cells, just as its yeast homolog.