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Human NOC3 is essential for DNA replication licensing in human cells.

Man-Hei Cheung1,2,3, Aftab Amin1,2,4, Rentian Wu1

  • 1a Division of Life Science, Center for Cancer Research and State Key Lab for Molecular Neuroscience , Hong Kong University of Science and Technology , Hong Kong , China.

Cell Cycle (Georgetown, Tex.)
|February 12, 2019
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Summary

Human Noc3 homolog (hNOC3) is crucial for DNA replication licensing by ensuring pre-replicative complex formation. Its knockdown causes replication defects and apoptosis, independent of ribosome biogenesis roles.

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DNA replicationFAD24NOC3Pre-RCreplication licensing

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Noc3p is vital for DNA replication licensing in yeast.
  • Human Noc3 homolog (hNOC3) has known roles in DNA replication and proliferation.
  • The specific role of hNOC3 in replication licensing remained unclear.

Purpose of the Study:

  • To elucidate the role of hNOC3 in human DNA replication licensing.
  • To investigate the interaction of hNOC3 with pre-replicative complex (pre-RC) proteins.
  • To determine if hNOC3's function in replication is linked to ribosome biogenesis.

Main Methods:

  • Investigated hNOC3 interactions with human pre-RC proteins.
  • Assessed hNOC3 association with replication origins.
  • Performed hNOC3 knockdown in HeLa cells to observe effects on pre-RC formation and DNA replication.
  • Compared effects of hNOC3 knockdown with inhibition of ribosome biogenesis.

Main Results:

  • hNOC3 physically interacts with multiple human pre-RC proteins and binds to replication origins.
  • hNOC3 knockdown disrupts chromatin association of hCDC6 and hMCM.
  • hNOC3 depletion leads to DNA replication defects, abortive S-phase, and apoptosis.
  • Inhibition of ribosome biogenesis did not cause similar cell cycle or replication defects.

Conclusions:

  • hNOC3 plays an essential role in pre-RC formation and DNA replication initiation in human cells.
  • hNOC3's function in replication licensing is independent of its role in ribosome biogenesis.
  • hNOC3 is a critical factor for maintaining genomic stability and cell proliferation.