Abstract
Maintenance of genomic integrity is essential for cell survival. Specifically, during DNA replication cells use a complex network of mechanisms that prevents genomic instability. Recently, we and others identified Wee1, a serine/threonine and tyrosine kinase, as a new modulator of the genomic stability during S phase. Loss of its activity causes a general DNA damage response activation and a decrease in replication fork speed. These effects are counteracted by the downregulation of the endonuclease complex Mus81-Eme1, showing a new link between this endonuclease and Wee1 during DNA replication. Here we discuss the function of Wee1 in genomic stability and its relationship with the Mus81-Eme1 complex.
Highlights
Different external and internal agents can cause genomic alterations that trigger a variety of mechanisms allowing the cell to repair the injuries or avoid its cell cycle progression
ATM responds to DNA double strand breaks (DSBs), while ATR is activated in response to a wider variety of DNA lesions such as UV-induced damage, replication stress and DSBs
Althought we demonstrated that Cdk2 is phosphorylated by Wee1 during S phase, we did not observe major changes in chromatin loading of replication proteins upon Wee1 depletion and we observed a quick DNA Damage Response (DDR) activation upon enzymatic inhibition of Wee1 in cells synchronized in S phase
Summary
Different external and internal agents can cause genomic alterations that trigger a variety of mechanisms allowing the cell to repair the injuries or avoid its cell cycle progression. Our results indicate that Wee1 is involved in regulating the Mus81-Eme1 endonuclease activity to avoid undesirable DNA breaks. Wee1 activity controlling genomic stability Wee1 is a well-known negative regulator of Cdks and a controller of cell cycle progression.
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