The content examines how the Srs2 DNA helicase regulates the downregulation of the DNA damage checkpoint (DDC) through antagonizing the RPA complex. The key highlights are:
Srs2 has multiple regulatory features, including phosphorylation sites, protein-protein interaction domains, and sumoylation sites.
Genetic analyses show that among these features, Srs2 binding to PCNA and its sumoylation contribute to the antagonism of RPA during DDC downregulation.
Srs2 binding to PCNA helps recruit it to ssDNA regions flanked by PCNA, allowing selective RPA removal. Srs2 sumoylation, which depends on its PCNA binding, further promotes RPA antagonism.
Srs2 sumoylation peaks after the maximal activation of the DDC kinase Mec1, and this modification requires Mec1 but not its S1964 autophosphorylation site.
The two-step regulation involving PCNA binding and sumoylation allows Srs2 to counter RPA and dampen the DDC in a temporally and spatially controlled manner, preventing premature checkpoint downregulation.
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by Fan,J., Dhin... at www.biorxiv.org 03-29-2024
https://www.biorxiv.org/content/10.1101/2024.03.28.587206v2Deeper Inquiries