Mitotic catenation is monitored and resolved by a PKCε-regulated pathway
Nicola Brownlow1, Tanya Pike1, Daniel Zicha2
1Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, 44 Lincolns Inn Fields, London WC2A 3LY, UK.
Nature Communications
|December 9, 2014
Summary
Protein kinase C epsilon (PKCε) prevents premature anaphase by delaying spindle assembly checkpoint (SAC) silencing when sister chromatids remain catenated, ensuring chromosome integrity.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Mitotic exit requires silencing of the spindle assembly checkpoint (SAC).
- Proper chromosome segregation depends on resolving sister chromatid catenation before anaphase.
- The mechanisms regulating SAC silencing in response to unresolved catenation are not fully understood.
Purpose of the Study:
- To investigate the role of protein kinase C epsilon (PKCε) in the metaphase response to sister chromatid catenation.
- To elucidate the pathway through which PKCε regulates SAC silencing and chromosome catenation resolution during mitosis.
Main Methods:
- Investigated mammalian cell responses to mitotic challenges.
- Utilized immunofluorescence microscopy to assess kinetochore protein localization (BubR1, Mad2) and chromosome bridging (PICH).
- Examined the effects of PKCε inhibition on mitotic progression and chromosome integrity.
Main Results:
- PKCε mediates a metaphase response to catenation, delaying SAC silencing.
- This delayed exit is characterized by BubR1-high and Mad2-low kinetochores.
- PKCε is essential for resolving mitotic catenanes; its inhibition leads to premature anaphase with chromosome bridging.
Conclusions:
- PKCε plays a critical role in preventing genomic instability when sister chromatid catenation is unresolved.
- The PKCε-controlled pathway ensures timely resolution of catenanes, safeguarding chromosome integrity during mitotic exit.
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