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Histone supply regulates S phase timing and cell cycle progression.
Ufuk Günesdogan1, Herbert Jäckle2, Alf Herzig3
1Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.
Histone supply regulates the cell cycle in eukaryotes. Insufficient histone production extends S phase and causes a G2 cell cycle arrest, preventing mitosis.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Eukaryotes package DNA into nucleosomes, comprising histone proteins.
- Nucleosomes are disrupted and reassembled during DNA replication.
- Control of chromatin assembly and its coordination with the cell cycle remain unclear.
Purpose of the Study:
- To investigate the role of histone supply in cell cycle regulation.
- To elucidate the mechanism linking histone availability to cell cycle progression.
Main Methods:
- Utilized a histone null mutation in Drosophila melanogaster.
- Employed transgenic histone genes to control histone supply levels.
Main Results:
- Histone supply levels directly regulate the duration of S phase.
- Lack of de novo histone supply prolongs S phase and induces G2 arrest.
- This arrest prevents entry into mitosis.
Conclusions:
- A novel cell cycle surveillance mechanism monitors nucleosome assembly.
- This mechanism operates independently of DNA repair pathways.
- It functions by suppressing CDC25 phosphatase (String) expression.
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