Abstract

The cell cycle requires cells to duplicate their chromatin, DNA, and histones, while retaining a subset of epigenetic marks, in a highly coordinated manner. The WEE1 kinase was identified as an important regulator during S phase, preventing entry into mitosis until DNA replication has been completed. Interestingly, WEE1 has also emerged as a key player in regulating histone synthesis. It phosphorylates histone H2B at tyrosine 37 in the nucleosomes found upstream of the histone gene cluster, and this suppresses histone transcription in late S phase. These observations highlight a dual role for WEE1 as both a mitotic gatekeeper and a surveyor of chromatin synthesis, providing a direct link between epigenetics and cell-cycle progression. Importantly, this link has implications for the design of novel epigenetic inhibitors targeting cancers that display elevated expression of this kinase.

Original languageEnglish
Pages (from-to)394-402
Number of pages9
JournalTrends in Genetics
Volume29
Issue number7
DOIs
StatePublished - Jul 2013

Keywords

  • Cancer
  • Cell cycle
  • Epigenetics
  • Histones
  • Tyrosine phosphorylation
  • WEE1

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