Related Experiment Video
Updated: Feb 3, 2026
Targeted in Situ Mutagenesis of Histone Genes in Budding Yeast
Published on: January 26, 2017
CDK phosphorylation regulates Mcm3 degradation in budding yeast
Kaori Yamamoto1, Nishiho Makino2, Masayoshi Nagai2
1Department of Science, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka, 422-8021, Japan.
Abstract:
Accurate regulation of activity and level of the MCM complex is critical for precise DNA replication and genome transmission. Cyclin-dependent kinase (CDK) negatively regulates nuclear localization of the MCM complex via phosphorylation of the Mcm3 subunit. More recently, we found that Mcm3 is degraded via the Skp1-Cullin-F-box (SCF)-proteasome axis in budding yeast. However, how Mcm3 degradation is regulated is largely unknown. Here, we show that CDK represses Mcm3 degradation. Phosphorylated Mcm3 was excluded from the nucleus, where SCF is predominantly located, although CDK-mediated phosphorylation itself generated a phosphodegron of Mcm3, stimulating the degradation of Mcm3 resident in the nucleus. Thus, CDK negatively regulated nuclear MCM levels by exclusion from the nucleus and degradation in the nucleus via Mcm3 phosphorylation. We will discuss the physiological importance of Mcm3 degradation.
Insights
Cyclin-dependent kinase (CDK) controls DNA replication by regulating the MCM complex. CDK phosphorylation of Mcm3 limits its nuclear presence and promotes its degradation, ensuring precise genome transmission.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Accurate regulation of the MCM complex is essential for DNA replication and genome stability.
- Cyclin-dependent kinase (CDK) influences MCM complex nuclear localization through Mcm3 subunit phosphorylation.
- Mcm3 is degraded by the Skp1-Cullin-F-box (SCF)-proteasome pathway, but its regulation remains unclear.
Purpose of the Study:
- To investigate the regulatory mechanisms governing Mcm3 degradation.
- To elucidate the role of CDK in regulating Mcm3 stability and nuclear levels.
- To understand how Mcm3 phosphorylation impacts its degradation and nuclear exclusion.
Main Methods:
- Budding yeast model system.
- Analysis of Mcm3 phosphorylation and degradation.
- Investigating the interplay between CDK, Mcm3, and the SCF-proteasome pathway.
- Cellular localization studies of MCM complex components.
Main Results:
- CDK negatively regulates Mcm3 degradation.
- CDK-mediated Mcm3 phosphorylation leads to nuclear exclusion.
- Phosphorylated Mcm3 is targeted for degradation within the nucleus via a phosphodegron mechanism.
- CDK controls nuclear MCM levels through both exclusion and degradation pathways.
Conclusions:
- CDK plays a dual role in negatively regulating nuclear MCM levels by promoting Mcm3 exclusion and degradation.
- Understanding Mcm3 degradation regulation is critical for precise DNA replication and genome integrity.
- This study reveals a novel regulatory mechanism for MCM complex homeostasis.
Related Concept Videos
02:58Regulated Protein Degradation
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
02:58Regulated Protein Degradation
01:45Positive Regulator Molecules
01:02Phosphorylation
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
01:23Negative Regulator Molecules
02:24Regulation of Expression Occurs at Multiple Steps
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...