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Ribonucleotide reductase--new twists in an old tale
J F Whitfield1, M Sikorska, T Youdale
1Biological Sciences Division, National Research Council of Canada, Ottawa.
Advances in Enzyme Regulation
|January 1, 1989
Summary
Liver cells regulate ribonucleotide reductase during proliferation. Following partial hepatectomy, cells activate M1 and M2 subunits to form holoenzyme for DNA replication, then degrade M1 post-S phase.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Adult rat liver cells are quiescent but express ribonucleotide reductase M1 subunits.
- These M1 subunits are rapidly inactivated and degraded due to low deoxyribonucleotide demand.
Purpose of the Study:
- To investigate the regulation of ribonucleotide reductase M1 and M2 subunits during liver regeneration.
- To understand the assembly and localization of active ribonucleotide reductase holoenzyme.
Main Methods:
- Analysis of M1 and M2 subunit expression and degradation.
- Enzyme activity assays.
- Cellular localization studies.
Main Results:
- Partial hepatectomy induces proliferation, leading to M2 subunit accumulation.
- M1 gene expression increases, inactivation and degradation decrease, forming active holoenzyme on the outer nuclear membrane.
- Post-S phase, M1 expression decreases, and degradation resumes; M1 fragments retain partial activity.
Conclusions:
- Liver regeneration involves coordinated regulation of ribonucleotide reductase subunits.
- Active holoenzyme formation is crucial for supplying deoxyribonucleotides for DNA replication.
- Dysregulation of M1 control is observed in cancer cells.