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 language | English |
---|---|
Pages (from-to) | 394-402 |
Number of pages | 9 |
Journal | Trends in Genetics |
Volume | 29 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2013 |
Keywords
- Cancer
- Cell cycle
- Epigenetics
- Histones
- Tyrosine phosphorylation
- WEE1