Histone supply regulates S phase timing and cell cycle progression

Elife. 2014 Sep 9;3:e02443. doi: 10.7554/eLife.02443.

Abstract

Eukaryotes package DNA into nucleosomes that contain a core of histone proteins. During DNA replication, nucleosomes are disrupted and re-assembled with newly synthesized histones and DNA. Despite much progress, it is still unclear why higher eukaryotes contain multiple core histone genes, how chromatin assembly is controlled, and how these processes are coordinated with cell cycle progression. We used a histone null mutation of Drosophila melanogaster to show that histone supply levels, provided by a defined number of transgenic histone genes, regulate the length of S phase during the cell cycle. Lack of de novo histone supply not only extends S phase, but also causes a cell cycle arrest during G2 phase, and thus prevents cells from entering mitosis. Our results suggest a novel cell cycle surveillance mechanism that monitors nucleosome assembly without involving the DNA repair pathways and exerts its effect via suppression of CDC25 phosphatase String expression.

Keywords: cell cycle control; chromatin assembly; histones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Blotting, Western
  • Cell Cycle / genetics*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Checkpoint Kinase 1
  • Chromatin Assembly and Disassembly / genetics
  • DNA Replication / genetics
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism
  • G2 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Regulation, Developmental
  • Histones / genetics*
  • Histones / metabolism
  • Mutation*
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • S Phase / genetics*
  • Time Factors
  • cdc25 Phosphatases / genetics
  • cdc25 Phosphatases / metabolism

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • Histones
  • Nucleosomes
  • Protein Kinases
  • Checkpoint Kinase 1
  • Mei-41 protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • Protein Tyrosine Phosphatases
  • cdc25 Phosphatases
  • stg protein, Drosophila