Dhingra N, Wei L, Zhao X

The DNA damage response relies on protein modifications to elicit physiological changes required for coping with genotoxic conditions. Besides canonical DNA damage checkpoint-mediated phosphorylation, DNA damage-induced SUMOylation has recently been shown to promote genotoxin survival. Crosstalk between these two pathways exists in both yeast and human cells. In particular, SUMOylation ...

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is required for optimal checkpoint function, but the underlying mechanisms are not well understood. To address this question, we examined the SUMOylation of the first responder to DNA lesions, the ssDNA-binding protein complex Replication protein A (RPA) in budding yeast (Saccharomyces cerevisiae). We delineated the SUMOylation sites of the RPA large subunit, Rfa1 on the basis of previous and new mapping data. Findings using a SUMOylation-defective Rfa1 mutant suggested that Rfa1 SUMOylation acts in parallel with the 9-1-1 checkpoint complex to enhance the DNA damage checkpoint response. Mechanistically, SUMOylated Rfa1 fostered an interaction with a checkpoint adaptor protein, Sgs1, and contributed to checkpoint kinase activation. Our results suggest that SUMO-based modulation of a DNA damage sensor positively influences the checkpoint response.

Date: Dec. 27, 2018

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