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Human replication protein Cdc6 is selectively cleaved by caspase 3 during apoptosis
Cristina Pelizon1, Fabrizio d'Adda di Fagagna, Lorena Farrace
1MCR Cancer Cell Unit, Hutchison/MRC Research Centre, Cambridge, UK. cpelizon@yahoo.co.uk
EMBO Reports
|August 2, 2002
Summary
Human Cdc6 (HuCdc6) protein is cleaved during apoptosis, preventing cell replication and promoting cell death. This cleavage is crucial for regulating cell proliferation and programmed cell death.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- DNA replication initiation in eukaryotes involves pre-replicative complex (pre-RC) assembly.
- Cdc6 protein is essential for pre-RC formation and chromatin binding, regulating DNA replication and cell proliferation.
Purpose of the Study:
- To investigate the role and fate of human Cdc6 (HuCdc6) during programmed cell death (apoptosis).
Main Methods:
- Studied HuCdc6 cleavage in human cell lines undergoing apoptosis induced by various stimuli.
- Utilized caspase-uncleavable mutant HuCdc6 to assess its impact on apoptosis.
Main Results:
- HuCdc6, unlike HuOrc2 and HuMcm5, undergoes specific cleavage during apoptosis across multiple human cell lines.
- Expression of a caspase-uncleavable HuCdc6 mutant delays apoptosis and cell death.
Conclusions:
- Cleavage of HuCdc6 is a critical event in apoptosis.
- This cleavage prevents replication in compromised cells, facilitating programmed cell death and maintaining genomic integrity.