Replication protein A (RPA) sumoylation positively influences the DNA damage checkpoint response in yeast Journal Article

   


Authors: Dhingra, N.; Wei, L.; Zhao, X.
Article Title: Replication protein A (RPA) sumoylation positively influences the DNA damage checkpoint response in yeast
Abstract: 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. Cross-talk between these two pathways exists in both yeast and human cells. In particular, sumoylation 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. © 2019 Dhingra et al.
Keywords: dna damage; saccharomyces cerevisiae; dna damage response; dna damage checkpoint; rpa; checkpoint control; small ubiquitin-like modifier (sumo); dna damage induced sumoylation; sumoylation, sgs1, checkpoint kinase activation
Journal Title: Journal of Biological Chemistry
Volume: 294
Issue: 8
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2019-02-22
Start Page: 2690
End Page: 2699
Language: English
DOI: 10.1074/jbc.RA118.006006
PUBMED: 30591583
PROVIDER: scopus
PMCID: PMC6393611
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062008409&doi=10.1074%2fjbc.RA118.006006&partnerID=40&md5=af9bc065014752af7adb1bffc6675def
Notes: Article -- Export Date: 1 April 2019 -- Source: Scopus
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MSK Authors
  1. Xiaolan Zhao
    77 Zhao
  2. Lei Wei
    11 Wei
  3. Nalini Dhingra
    10 Dhingra
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