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Trends Genet. 2013 Jul;29(7):394-402. doi: 10.1016/j.tig.2013.02.003. Epub 2013 Mar 26.

WEE1 tyrosine kinase, a novel epigenetic modifier.

Author information

1
Drug Discovery Department, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA. kiran.mahajan@moffitt.org

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.

PMID:
23537585
PMCID:
PMC3700603
DOI:
10.1016/j.tig.2013.02.003
[Indexed for MEDLINE]
Free PMC Article

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