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Updated: Jun 22, 2026

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms
1Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA. satya@ncifcrf.gov
Abstract:
After a decade of extensive work on gene knockout mouse models of cell-cycle regulators, the classical model of cell-cycle regulation was seriously challenged. Several unexpected compensatory mechanisms were uncovered among cyclins and Cdks in these studies. The most astonishing observation is that Cdk2 is dispensable for the regulation of the mitotic cell cycle with both Cdk4 and Cdk1 covering for Cdk2's functions. Similar to yeast, it was recently discovered that Cdk1 alone can drive the mammalian cell cycle, indicating that the regulation of the mammalian cell cycle is highly conserved. Nevertheless, cell-cycle-independent functions of Cdks and cyclins such as in DNA damage repair are still under investigation. Here we review the compensatory mechanisms among major cyclins and Cdks in mammalian cell-cycle regulation.
Insights
Cyclin-dependent kinases (Cdks) and cyclins exhibit compensatory mechanisms in cell-cycle regulation. Notably, Cdk2 is dispensable, with Cdk1 and Cdk4 compensating for its functions in mammalian cell division.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The classical model of cell-cycle regulation has been challenged by recent findings.
- Gene knockout mouse models have revealed unexpected compensatory mechanisms among cell-cycle regulators.
Purpose of the Study:
- To review compensatory mechanisms among major cyclins and cyclin-dependent kinases (Cdks) in mammalian cell-cycle regulation.
- To highlight the dispensability of Cdk2 and the conserved nature of cell-cycle control.
Main Methods:
- Review of existing literature on gene knockout mouse models.
- Analysis of studies investigating compensatory mechanisms in cyclins and Cdks.
- Examination of Cdk1's role in driving the mammalian cell cycle.
Main Results:
- Cdk2 is dispensable for mitotic cell-cycle regulation in mammals.
- Cdk4 and Cdk1 compensate for Cdk2's functions.
- Cdk1 alone can drive the mammalian cell cycle, similar to yeast.
Conclusions:
- Mammalian cell-cycle regulation is highly conserved, with Cdk1 playing a central role.
- Compensatory mechanisms among Cdks and cyclins are crucial for cell-cycle control.
- Cell-cycle-independent functions of Cdks and cyclins, including DNA damage repair, require further investigation.
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